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Enzyme Nomenclature
Information on EC 2.7.11.1 - non-specific serine/threonine protein kinase and Organism(s) Homo sapiens
for references in articles please use BRENDA:EC2.7.11.1
Word Map on EC 2.7.11.1
- 2.7.11.1
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mapks
-
signal-regulated
- carcinoma
- injury
- arrest
- cardiac
- endothelial
- rapamycin
- vascular
- repair
- forskolin
-
synaptic
- inflammation
- parkinsonism
- diabetes
- dysfunction
- adhesion
-
phorbol
- hippocampal
- alzheimer
-
autophosphorylation
-
cyclin
- caspase-3
- metastasis
- neurodegenerative
-
neuroprotective
- wortmannin
-
adenylyl
- tumorigenesis
-
memory
- myocytes
-
gtpases
-
double-stranded
-
nf-kappab
- phosphoprotein
-
beta-catenin
- dopamine
- cardiomyocytes
-
cyclin-dependent
-
dominant-negative
- nmda
-
postsynaptic
-
hyperphosphorylation
-
anti-apoptotic
-
okadaic
- isoproterenol
- staurosporine
-
beta-adrenergic
- 13-acetate
-
l-type
- drug development
- medicine
- molecular biology
- pharmacology
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Specify your search results
The taxonomic range for the selected organisms is: Homo sapiens
The enzyme appears in selected viruses and cellular organisms
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EC NUMBER 
COMMENTARY 
2.7.11.1
-
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RECOMMENDED NAME
GeneOntology No.
non-specific serine/threonine protein kinase
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
ATP + a protein = ADP + a phosphoprotein
catalytic mechanism and regulation of PKN
-
ATP + a protein = ADP + a phosphoprotein
the CK1 family shows a strong preference both in vitro and in vivo for primed, pre-phosphorylated substrates. CK1 family members prefer acidic substrates in vitro, most notably those with acidic residues in the N-3 position, e.g. D-X-X-S/T. The most effective motif contains a phospho-residue in the N-3 position, such as pS/pT-X-X-S/T, where pS/pT refers to a phospho-serine or phospho-threonine, X refers to any amino acid, and the underlined residues refer to the target site
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
phospho group transfer
-
-
-
-
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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.
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CAS REGISTRY NUMBER
COMMENTARY
191808-15-8
phosphoinositide dependent protein kinase 1
340830-03-7
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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
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
SwissProt
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660602, 660948, 661422, 661900, 662134, 662175, 662260, 662261, 662313, 662388, 662601, 662674, 662737, 662817, 662855, 662912, 671945, 672431, 672994, 673433, 674068, 676261, 677245, 691623, 691787, 693361, 694964, 695048, 707574, 708246, 708371, 708481, 708760, 709179, 710035, 722389, 722418, 722795, 723080, 737936, 737970, 738003, 738688, 739116, 739247, 739704, 739715, 739739, 742242, 742890, 743408, 743837, 743877
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at least 3 different isozymes PKNalpha/PKN-1/PAK-1, PKNbeta, and PRK2/PKNgamma/PAK-2
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small intestine SPAK-like kinase; intestinal inflammation-associated colonic epithelial isozyme
SwissProt
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GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
malfunction
metabolism
physiological function
additional information
evolution
human serine/threonine kinase ULK3 is annotated as belonging to unc-51-like family of serine/threonine kinases, but shares similarity with STK36 and dFu proteins
evolution
-
CK1 belongs to the CK1 family of serine/threonine kinases, CK1 is evolutionary conserved within eukaryotes
evolution
the enzyme is a member of the family of phosphatidylinositol-3 kinase-related kinases (PIKKs). All of these can interact with different membrane mimetics and may have different preferences only for membrane properties such as surface charge, curvature, and lipid packing. The FATC domain is shared by all members of the family and plays an important role for the regulation of each PIKK. Sequence conservation of the FATC domain; the enzyme is a member of the family of phosphatidylinositol-3 kinase-related kinases (PIKKs). All of these can interact with different membrane mimetics and may have different preferences only for membrane properties such as surface charge, curvature, and lipid packing. The FATC domain is shared by all members of the family and plays an important role for the regulation of each PIKK. Sequence conservation of the FATC domain; the enzyme is a member of the family of phosphatidylinositol-3 kinase-related kinases (PIKKs). All of these can interact with different membrane mimetics and may have different preferences only for membrane properties such as surface charge, curvature, and lipid packing. The FATC domain is shared by all members of the family and plays an important role for the regulation of each PIKK. Sequence conservation of the FATC domain; the enzyme is a member of the family of phosphatidylinositol-3 kinase-related kinases (PIKKs). All of these can interact with different membrane mimetics and may have different preferences only for membrane properties such as surface charge, curvature, and lipid packing. The FATC domain is shared by all members of the family and plays an important role for the regulation of each PIKK. Sequence conservation of the FATC domain
evolution
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STK38 is a member of the NDR family, which functions in cell-cyclerelated processes
evolution
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casein kinase 1delta (CK1dellta) is an evolutionarily conserved serine/threonine kinase
malfunction
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downregulation of ZIP kinase is associated with tumor invasion, metastasis and poor prognosis in gastric cancer
malfunction
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STK11 has been identified as a large-scale deletion in a patient with schizophrenia and Peutz-Jeghers syndrome
malfunction
kinase-deficient mutants of ULK3 are inactive in regulation of GLI protein activity
malfunction
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Pim-2 short interfering RNA reduces mutiple myeloma cell viability in cocultures with bone marrow stromal cells and osteoclasts. Pim-2 inhibition suppresses mutiple myeloma cell survival, cooperatively with rapamycin
malfunction
chemical inhibition, siRNA, and expression of dominant-negative p110alpha are all associated with increased AMPK T172 phosphorylation, whereas expression of constitutively-active p110alpha reduces T172 phosphorylation. Pharmacological inhibition of p110a reduces AMPK S485/491 phosphorylation, while constitutively-active p110alpha increases AMPK S485/491 phosphorylation. In response to oligomycin or serum starvation, AMPK T172 phosphorylation is elevated in p110alpha-deficient myoblasts compared to control myoblasts. p110alpha deficiency modifies AMPK responses to cellular stress
malfunction
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enzyme silencing suppresses self-renewal, motility, tumorigenesis, and radioresistance of mesenchymal glioma stem cells via a loss of the mesenchymal signature
malfunction
isoproterenol-induced EGFR transactivation is abolished in PI3Kgamma null mutants or through enzyme inhibition by wortmannin or LY-294002
malfunction
Blockade of p110alpha by RNA interference or multiple independent PI3K inhibitors not only blocks Ser585 phosphorylation in cytokine-dependent cells and primary human AML blasts, but also results in a block in survival signaling and cell death
malfunction
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when CK2 is suppressed in white adipocytes, either by RNAi or a pharmacological approach using the CK2 inhibitor CX-4945, there occurs a robust induction of Ucp1 and several other brown selective genes such as Cidea, Cited1, and Elov3. Phosphorylation of class I HDACs, HDAC1 and HDAC2, is strikingly reduced by CK2 inhibition in white adipocytes, consistent with increased browning, since inhibition of class I HDACs is linked to increased expression of PGC1alpha
malfunction
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the cellular depletion of STK38 has no effect on the G1-phase transition under normal conditions, but leads to a slight increase in G1 arrest after X-ray irradiation. The depletion of STK38 alone may be insufficient to activate the G1 checkpoint. STK38 depletion has no effect on the distribution of cells in S-phase under normal conditions
malfunction
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CK2 inhibition or protein phosphatase 2A activation decrease NS2 phosphorylation
malfunction
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inhibition of casein kinase 1 delta blocks primary ciliogenesis in human telomerase reverse transcriptase immortalized retinal pigmented epithelial cells. Overexpression of an AKAP450 fragment containing the CK1delta-binding site inhibits Golgi-derived microtubule nucleation, Golgi distribution of intraflagellar transport protein 20 homologue, and ciliogenesis. CK1delta inhibition also alters pericentrosomal or ciliary distribution of several proteins involved in ciliary transport, including centrosomal protein of 290 kDa, pericentriolar material protein 1, and polycystin-2, as well as the Golgi distribution of its binding partner, A-kinase anchor protein 450 (AKAP450). AKAP450 distribution is dispersed by CK1delta inhibition. Knockdown of CK1delta in hTERT-RPE cells stably expressing GFP-tagged IFT20 disrupts the intracellular distribution of IFT20, consistent with perturbation of the GM130 staining pattern
malfunction
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pharmacological inhibition or genetic ablation of CK2 blocks the phosphorylation of OTUB1 at Ser16 and its nuclear localization in various cells
metabolism
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baicalin triggers autophagy through inhibition of the AKT signaling pathway in T-24 cells, overview
metabolism
the enzyme is involved in isoproterenol-induced EGFR transactivation. PI3K is required for beta2AR-stimulated EGFR transactivation
metabolism
-
the enzyme is a regulator of the subcellular trafficking and stability of organic anion transporting polypeptide 1A2
metabolism
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casein kinase 1 is responsible for the basolateral localization of the Ca2+-activated non-selective cation channel TRPM4
physiological function
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protein kinase Balpha is involved in inositol lipid signalling, a pleckstrin homology (PH) domain binds phosphatidylinositol 3,4,5-trisphosphate which is required for PKB phosphorylation and activation
physiological function
-
PKA activity, without directly phosphorylating P2X(4)R, markedly enhances ATP-stimulated P2X(4)R currents and hence cytosolic Ca2+ signals
physiological function
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DAP-kinase is an essential regulator of autophagy, DAP-kinase is a tumor suppressor that mediates several cell death pathways, such as apoptosis and programmed necrosis
physiological function
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ZIPK is a tumor suppressor and plays an important role in gastric carcinoma development through its pro-apoptotic function
physiological function
-
protein kinase D1 regulates cofilin-mediated F-actin reorganization and cell motility via slingshot, protein kinase D1 inhibits barbed end formation and directed cell migration
physiological function
the serine/threonine kinase ULK3 acts as a positive regulator of Hedgehog pathway and Gli proteins, ULK3 catalytical activity is crucial for its function in SHH pathway, overview. The Hedgehog signaling pathway plays crucial roles in embryonic development and is implicated in tissue homeostasis maintenance and neurogenesis in adults. ULK3 enhances endogenous and overexpressed GLI1 and GLI2 transcriptional activity in cultured cells, and ULK3 kinase activity is required for nuclear translocation of GLI1 from cytosol
physiological function
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the CK1 family of serine/threonine kinases regulates diverse cellular processes, including circadian rhythms, Wnt signaling, membrane trafficking, cytoskeleton maintenance, DNA replication, DNA damage response, RNA metabolism and parasitic infections, through binding to and phosphorylation a myriad of protein substrates. CK1 isoforms are key regulators of several cellular growth and survival processes, including Wnt and Hedgehog signaling, cell cycle control, DNA repair and apoptosis. CK1 is involved in scaffold binding and kinase regulation in Wnt signaling and circadian rhythms. CK1is itself regulated by posttranslationalmodification, including autophosphorylation. CK1alpha is a essential component of the Wnt/beta-catenin signaling pathway. It binds to axin, and phosphorylates beta-catenin on serine 45, thereby creating a GSK3 recognition site and ultimately causing the degradation of beta-catenin. CK1delta/epsilon are implicated in colon, pancreatic and breast cancer progression via the suppression of apoptosis, regulation of mitotic function, and/or activation of beta-catenin signaling. CK1epsilon is a pro-survival factor in cancer cells in vitro
physiological function
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LKB1 is a key signaling kinase that regulates cellular growth
physiological function
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upregulation of Pim-2 is an anti-apoptotic mechanism for mutiple myeloma cell survival
physiological function
AMP-activated protein kinase (AMPK) is a serine/threonine kinase that functions as a sensor of intracellular energy. Activation of AMPK is associated with increased phosphorylation of the alpha-subunit at threonine 172 and decreased phosphorylation at serine 485 in AMPKalpha1 and serine 491 in AMPKalpha2 (S485/491). p110alpha-mediated phosphorylation of AMPKa at S485/491 is Akt-dependent
physiological function
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the enzyme binds and phosphorylates the nuclear factor-kappaB regulator IKKalpha, leading to activation of nuclear factor-kappaB signaling in glioma stem cells
physiological function
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serine-threonine kinase 38 regulates CDC25A stability and the DNA damage-induced G2/M checkpoint
physiological function
the generation of phosphatidylinositol (3,4,5)-tris-phosphate (PIP3) by the lipid kinase function stabilizes beta2AR-EGFR complexes while the protein kinase activity of PI3K regulates Src activation by direct phosphorylation. Phosphorylation of Src by phosphoinositide 3-kinase regulates beta-adrenergic receptor-mediated EGFR transactivation. EGFR transactivation is a mechanism by which the EGF receptor is stimulated, internalized, and downstream signaling initiated following agonist stimulation by a GPCR, such as the beta-adrenergic receptor. The protein kinase activity of PI3K phosphorylates serine residue 70 on Src to enhance its activity and induce EGFR transactivation following beta-adrenergic receptor stimulation. This additional function for PI3K, whereby Src is a substrate for the protein kinase activity of enzyme PI3K, is of importance since Src plays a key role in pathological and physiological signaling
physiological function
the enzyme is important for DNA damage response and signaling in the presence of DNA damages; the enzyme is important for DNA damage response and signaling in the presence of DNA damages; the enzyme is important for DNA damage response and signaling in the presence of DNA damages; the enzyme is important for DNA damage response and signaling in the presence of DNA damages
physiological function
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casein kinase 2 activity is important for bluetongue virus replication and for regulating VIB morphology during bluetongue virus infection
physiological function
phosphoinositide 3-kinase (PI3K) is a dual specificity kinase that is known to be involved in cell survival and malignant transformation, and it is able to phosphorylate both lipid and protein substrates. PI3K protein kinase activity can directly phosphorylate growth factor receptors on human hematopoietic (blood) cells to promote a survival-only response. The protein kinase activity but not the lipid kinase activity of PI3K promotes cytokine-mediated cell survival. It phosphorylates serine residues in the cytoplasmic portion of cytokine receptors to promote hemopoietic cell survival. The PI3K lipid kinase activity is not essential for regulating cell survival
physiological function
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the enzyme regulates hematopoietic stem cell proliferation and survival
physiological function
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casein kinase 2 (CK2) is a suppressor of brown adipocyte formation, role of CK2 as a repressor of browning in adipose tissue, overview. Expression/suppression of CK2 is involved in how adipose tissue regulates its cellular composition of brown versus white adipocytes
physiological function
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serine-threonine kinase 38 regulates CDC25A stability and the DNA damage-induced G2/M checkpoint. Enzyme STK38 is required for CDC25A degradation. Phosphorylation of Ser76 by STK38 regulates CDC25A's stability. Wild-type CDC25A is rapidly degraded, whereas the S76A mutant remains stable. STK38 is not involved in regulating the S-phase checkpoint, but enzyme CHK1 regulates the S-phase checkpoint by phosphorylating CDC25A at a number of sites, including Ser124. While CHK1 phosphorylates CDC25A at multiple sites, STK38's phosphorylation of CD25A may be more limited
physiological function
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human host cell CK2 activity is important for bluetongue virus (BTV) replication. Host cell factor, protein phosphatase 2A, PP2A, is involved in NS2 dephosphorylation and, together with CK2, regulates viral inclusion bodies, VIBs, morphology and virus replication. Viral VIBs are predominantly comprised of a BTV-encoded non-structural protein 2, NS2. The two host enzymes influence the dynamic nature of VIB assembly/disassembly, and these concerted activities may be relevant to the assembly and the release of these cores from VIBs
physiological function
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casein kinase 1delta functions at the centrosome and Golgi to promote ciliogenesis. CK1delta functions to coordinate the positioning and activity of multiple ciliary effectors, such as Rab11a and Rab8a, CEP290, PCM1, and IFT20, to mediate transport of polycystin-2 and other membrane cargo from the Golgi to the basal body and nascent cilium. CK1delta is required for microtubule nucleation at the Golgi and maintenance of Golgi integrity. CK1delta mediates primary ciliogenesis by multiple mechanisms, one involving its centrosomal function and another dependent on its interaction with AKAP450 at the Golgi, where it is important for maintaining Golgi organization and polarized trafficking of multiple factors that mediate ciliary transport
physiological function
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casein kinase 1 (CK1) phosphorylates S839 and is responsible for the basolateral localization of transient receptor potential melastatin-like 4, TRPM4, a plasma membrane Ca2+-activated non-selective cation channel expressed in a wide range of human tissues. TRPM4 participates in a variety of physiological processes such as T cell activation, myogenic vasoconstriction, and allergic reactions. Role for S839 phosphorylation in the basolateral expression of TRPM4 channels in epithelial cells. Human TRPM4 contains about 130 serine and threonine and about 27 tyrosine residues in its sequence that can be potentially phosphorylated by different kinases. CK1 activity regulates TRPM4 basolateral localization
physiological function
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casein kinase 2 (CK2) phosphorylates the deubiquitylase OTUB1 at Ser16 to trigger its nuclear localization and accumulation. OTUB1 is a member of the ovarian tumor domain protease (OTU) family of deubiquitylating enzymes (DUBs). DUBs are isopeptidases that remove attached ubiquitin chains or molecules from their targets. OTUB1 functions in deubiquitylating K48-linked ubiquitin chains as well as inhibiting the action of E2 ubiquitin-conjugating enzymes. The phosphorylation of OTUB1 at Ser16 does not alter its catalytic activity in vitro and the interactions with UBE2N. But the phosphorylation at Ser16 and subsequent nuclear localization of OTUB1 is essential for cells to repair ionizing radiation-induced DNA damage in osteosarcoma U2OS cells. Phosphorylation-dependent recruitment of OTUB1 to its other targets may also be likely. Phosphorylation of OTUB1 at Ser16 impacts IR-induced DNA-damage repair. Nuclear localization of OTUB1 may be necessary for DSB-induced 53BP1 foci formation
physiological function
important role of Pim1 kinase in regulating hematopoietic stem cell (HSC) cell proliferation and survival, and relative role of individual Pim kinase in hematopoietic stem cell functions and regulation, overview
additional information
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structure of catalytic sites of CK1 isozymes, overview. A spontaneously occurring human mutation of a CK1 priming site in PER2, Ser662, leads to decreased phosphorylation of stabilizing sites in PER2 and accelerated circadian rhythms
additional information
characterization and comparisons of the interactions with lipids and different membrane mimetics for the FATC domains of human DNA-PKcs, human ATM, human ATR, human SMG-1, and human TRRAP by NMR and CD spectroscopy, overview; characterization and comparisons of the interactions with lipids and different membrane mimetics for the FATC domains of human DNA-PKcs, human ATM, human ATR, human SMG-1, and human TRRAP by NMR and CD spectroscopy, overview; characterization and comparisons of the interactions with lipids and different membrane mimetics for the FATC domains of human DNA-PKcs, human ATM, human ATR, human SMG-1, and human TRRAP by NMR and CD spectroscopy, overview; characterization and comparisons of the interactions with lipids and different membrane mimetics for the FATC domains of human DNA-PKcs, human ATM, human ATR, human SMG-1, and human TRRAP by NMR and CD spectroscopy, overview
additional information
characterization and comparisons of the interactions with lipids and different membrane mimetics for the FATC domains of human DNA-PKcs, human ATM, human ATR, human SMG-1, and human TRRAP by NMR and CD spectroscopy, overview; characterization and comparisons of the interactions with lipids and different membrane mimetics for the FATC domains of human DNA-PKcs, human ATM, human ATR, human SMG-1, and human TRRAP by NMR and CD spectroscopy, overview; characterization and comparisons of the interactions with lipids and different membrane mimetics for the FATC domains of human DNA-PKcs, human ATM, human ATR, human SMG-1, and human TRRAP by NMR and CD spectroscopy, overview; characterization and comparisons of the interactions with lipids and different membrane mimetics for the FATC domains of human DNA-PKcs, human ATM, human ATR, human SMG-1, and human TRRAP by NMR and CD spectroscopy, overview
additional information
characterization and comparisons of the interactions with lipids and different membrane mimetics for the FATC domains of human DNA-PKcs, human ATM, human ATR, human SMG-1, and human TRRAP by NMR and CD spectroscopy, overview; characterization and comparisons of the interactions with lipids and different membrane mimetics for the FATC domains of human DNA-PKcs, human ATM, human ATR, human SMG-1, and human TRRAP by NMR and CD spectroscopy, overview; characterization and comparisons of the interactions with lipids and different membrane mimetics for the FATC domains of human DNA-PKcs, human ATM, human ATR, human SMG-1, and human TRRAP by NMR and CD spectroscopy, overview; characterization and comparisons of the interactions with lipids and different membrane mimetics for the FATC domains of human DNA-PKcs, human ATM, human ATR, human SMG-1, and human TRRAP by NMR and CD spectroscopy, overview
additional information
characterization and comparisons of the interactions with lipids and different membrane mimetics for the FATC domains of human DNA-PKcs, human ATM, human ATR, human SMG-1, and human TRRAP by NMR and CD spectroscopy, overview; characterization and comparisons of the interactions with lipids and different membrane mimetics for the FATC domains of human DNA-PKcs, human ATM, human ATR, human SMG-1, and human TRRAP by NMR and CD spectroscopy, overview; characterization and comparisons of the interactions with lipids and different membrane mimetics for the FATC domains of human DNA-PKcs, human ATM, human ATR, human SMG-1, and human TRRAP by NMR and CD spectroscopy, overview; characterization and comparisons of the interactions with lipids and different membrane mimetics for the FATC domains of human DNA-PKcs, human ATM, human ATR, human SMG-1, and human TRRAP by NMR and CD spectroscopy, overview
additional information
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overexpression of microRNA miR-455 decreases protein expression of RAF proto-oncogene serine/threonine-protein kinase (RAF1) but has no effect on mRNA level. miR-455 regulates RAF1 expression directly. Overexpression of miR-455 significantly inhibits the proliferation and the invasion of SW480, but has no effect on apoptosis. Overexpression of RAF1 partially reverses the inhibitory effect of miR-455 on the growth and the invasion of SW-480. MicroRNAs (miRNAs) are a class of small (18-25 nucleotides long) noncoding RNAs with important posttranscriptional regulatory functions. miRNAs play important roles in various physiological and pathological processes including carcinogenesis in various solid cancers including colorectal cancer
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
ATP + ABCA1 NBD1-R1 protein
ADP + phosphorylated ABCA1 NBD1-R1 protein
-
substrate protein is a recombinant construct of wild-type and mutant nucleotide binding domain 1 and cytoplasmic domain R1 of ATP-binding cassette transporter protein A1 expressed in Escherichia coli, phosphorylation at T1242, T1243, and S1255
-
-
?
ATP + ABCA1 NBD2-R2 protein
ADP + phosphorylated ABCA1 NBD2-R2 protein
-
substrate protein is a recombinant construct of wild-type and mutant nucleotide binding domain 2 and cytoplasmic domain R2 of ATP-binding cassette transporter protein A1 expressed in Escherichia coli
-
-
?
ATP + Ac-RPRAASF
ADP + Ac-Ac-RPRAApSF
-
an efficient fluorescence assay for serine/threonine kinases using a peptide array is developed. Assay is based on chemical reactions specific to phosphoserine and phosphothreonine residues, that is, base-mediated beta-elimination of the phosphate group and subsequent Michael addition of a thiol-containing fluorescent reagent. This procedure enables the covalent introduction of a fluorescent moiety into the phosphorylated peptide. Novel fluorescent reagents are designed for this purpose and synthesized
-
-
?
ATP + acetyl-CoA carboxylase
ADP + phosphorylated acetyl-CoA carboxylase
-
phosphorylation and inactivation
-
-
?
ATP + adenomatous polyposis coli protein
ADP + phosphorylated adenomatous polyposis coli protein
-
i.e. APC, APC is phosphorylated in vitro by CKIdelta and CKIepsilon
-
-
?
ATP + AIB1 protein
ADP + phosphorylated AIB1 protein
-
phosphorylation at S601 by isozyme CK1delta
-
-
?
ATP + alpha-casein
ADP + phosphorylated alpha-casein
-
casein kinase 1alpha
-
-
?
ATP + AMP-activated protein kinase alpha1
ADP + phospho-AMP-activated protein kinase
phosphorylation of Ser485 at subunit alpha1 and of Ser491 at subunit alpha2
-
-
?
ATP + ataxin-3 protein
ADP + phosphorylated ataxin-3 protein
-
phosphorylation at serines 340 and 352
-
-
?
ATP + BAF170
ADP + phosphorylated BAF170
-
BAF170 is a hSWI/SNF protein that contains one Akt consensus site
-
-
?
ATP + beta-hydroxy beta-methylglutaryl-coenzyme A reductase
ADP + phosphorylated beta-hydroxy beta-methylglutaryl-coenzyme A reductase
-
phosphorylation and inactivation
-
-
?
ATP + calmodulin
ADP + phosphorylated calmodulin
-
phosphorylation by isozyme CK1alpha
-
-
?
ATP + CARMA1 protein
ADP + phosphorylated CARMA1
-
i.e. CARD11 protein, phosphorylation at S608 by isozyme CK1alpha
-
-
?
ATP + Cdc42Hs
ADP + ?
PAK4 interacts only with the activated form of Cdc42Hs through its GTPase-binding domain
-
-
?
ATP + Cdk2 interacting protein
ADP + phosphorylated Cdk2 interacting protein
-
-
-
-
?
ATP + cell division cycle 7
ADP + phosphorylated cell division cycle 7
-
-
-
-
?
ATP + Dnmt1 protein
ADP + phosphorylated Dnmt1 protein
-
phosphorylation at S147 by isozymes CK1delta and CK1epsilon
-
-
?
ATP + FADD protein
ADP + phosphorylated FADD protein
-
phosphorylation at S194 by isozyme CK1alpha
-
-
?
ATP + Gli2 protein
ADP + phosphorylated Gli2 protein
high activity
-
-
?
ATP + glycogen synthase kinase-3 (GSK-3) fusion protein
ADP + phosphorylated- glycogen synthase kinase-3 fusion protein
-
-
-
-
?
ATP + granulocyte macrophage colony stimulating factor receptor
ADP + phospho-granulocyte macrophage colony stimulating factor receptor
ATP + histone H2A
ADP + phosphorylated histone H2A
recombinant human substrate, substrate of SSTK
-
-
?
ATP + histone H2AX
ADP + phosphorylated histone H2AX
recombinant human substrate, substrate of SSTK
-
-
?
ATP + histone H2B
ADP + phosphorylated histone H2B
recombinant human substrate, substrate of SSTK
-
-
?
ATP + histone H4
ADP + phosphorylated histone H4
recombinant substrate from Xenopus laevis, substrate of SSTK
-
-
?
ATP + IFNAR1 protein
ADP + phosphorylated IFNAR1 protein
-
phosphorylation at S535 by isozyme CK1alpha
-
-
?
ATP + KKRNRRLSVA
ADP + KKRNRRL-phosphoserine-VA
-
peptide substrate of NDR1
-
-
?
ATP + KLP10A protein
ADP + phosphorylated KLP10A protein
-
phosphorylation at S573 by isozyme CK1alpha
-
-
?
ATP + M3-muscarnic receptor
ADP + phosphorylated M3-muscarnic receptor
-
-
-
-
?
ATP + MCM2
ADP + ?
-
wild-type huCdc7 protein expressed in COS7 cells phosphorylates MCM2 and MCM3 proteins in vitro
-
-
?
ATP + MCM3
ADP + ?
-
wild-type huCdc7 protein expressed in COS7 cells phosphorylates MCM2 and MCM3 proteins in vitro
-
-
?
ATP + non-structural protein 2
ADP + phospho-non-structural protein 2
-
non-structural protein 2 from bluetongue virus (BTV)
-
-
?
ATP + non-structural protein 2
ADP + phosphorylated non-structural protein 2
-
-
-
-
?
ATP + NS5A protein
ADP + phosphorylated NS5A protein
-
recombinant NS5A expressed in Sf9 cells, substrate is a hepatitis C virus protein playing a critical role in virus replication and conferring interferon resistance to the virus, the viral protein is phosphorylated by several STE or AGC type protein kinases CK2, AKT1, SGK1, 90S6K, STE, phosphorylation patterns, overview
-
-
?
ATP + OTUB1
ADP + phospho-OTUB1
-
OTUB1 is a tumor domain protease, phosphorylation at Ser16, in GSDSEGVN
-
-
?
ATP + OTUB1 protein
ADP + phosphorylated OTUB1 protein
-
phosphorylation at serine 16
-
-
?
ATP + OTUD5 protein
ADP + phosphorylated OTUD5 protein
-
phosphorylation at serine 177
-
-
?
ATP + peptide LRRKtide
ADP + phosphorylated peptide LRRKtide
-
high activity towards the peptidic substrate LRRKtide
-
-
?
ATP + PHLPP1 protein
ADP + phosphorylated PHLPP1 protein
-
phosphorylation at T851 by isozyme CK1alpha
-
-
?
ATP + phosphoglycogen synthase peptide 2
ADP + phosphorylated phosphoglycogen synthase peptide 2
-
-
-
-
?
ATP + PKD2 protein
ADP + phosphorylated PKD2 protein
-
phosphorylation at S244 by isozymes CK1alpha, CK1delta, and CK1epsilon
-
-
?
ATP + protein
ADP + protein tyrosine phosphate
phosphorylates and inactivates the actin binding/depolymerizing factor cofilin and induces actin cytoskeletal changes
-
-
?
ATP + protein kinase C
ADP + phosphorylated protein kinase C
-
isozyme PKNalpha
-
-
?
ATP + rapamycin
ADP + phospho-rapamycin
-
-
-
?
ATP + Rec8 protein
ADP + phosphorylated Rec8 protein
-
phosphorylation at S412 by isozyme CK1delta and CK1epsilon, and at S400, S402, S404, S410, T414, and S416
-
-
?
ATP + RRRDDDSDDD
ADP + RRRDDDphosphoSDDD
-
a CK2-specific synthetic peptide substrate
-
-
?
ATP + RRRLSSLRA
ADP + RRRLSpSLRA
-
enzyme activities are determined by measuring initial velocities for His6-S6K1aII(DELTA AID)-T389E catalyzed phosphorylation of a commercially available S6K/RSK model peptide substrate 1 (S6K1-Tide, RRRLSSLRA)
-
-
?
ATP + RSRSRSRSRSRSPPPVSK
ADP + phosphorylated RSRSRSRSRSRSPPPVSK
-
SC35-derived peptide 180-197, recombinant GSK-3beta
-
-
?
ATP + SLR1 protein
ADP + phosphorylated SLR1 protein
-
phosphorylation at S196 and SS510
-
-
?
ATP + Snail protein
ADP + phosphorylated Snail protein
-
phosphorylation at S104 and S07 by isozyme CK1epsilon
-
-
?
ATP + SR protein
ADP + ?
enzyme plays a role as a co-repressor for homeodomain transcription factors
-
-
?
ATP + SSH1L protein
ADP + SSH1L phosphoprotein
-
PKD1 phosphorylates the SSH enzyme SSH1L at serine 978
-
-
?
ATP + TRPM4
ADP + phospho-TRPM4
-
i.e. transient receptor potential melastatin-like 4, phosphorylation at Ser839
-
-
?
ATP + TRPM4 protein
ADP + phosphorylated TRPM4 protein
-
phosphorylation at serine 839
-
-
?
ATP + Varicella-Zoster viral gB protein
ADP + phosphorylated Varicella-Zoster viral gB protein
-
phosphorylation at S34 in the sequence QSEDIT
-
-
?
ATP + YAP protein
ADP + phosphorylated YAP protein
-
phosphorylation at S384 and S387 by isozymes CK1delta and CK1epsilon
-
-
?
ATP + [FRAT-2 protein]
ADP + phosphorylated [FRAT-2 protein]
-
i.e. frequently rearranged in advanced T-cell lymphoma protein 2, phosphorylation by GSK3beta
-
-
?
ATP + [M3 muscarinic acetylcholine receptor]
ADP + phospho-[M3 muscarinic acetylcholine receptor]
-
recombinant substrate expressed in HEK-293 and CHO cells, casein kinase 1alpha
-
-
?
ATP + a protein
ADP + a phosphoprotein
-
in some cancers displaying chromosomal instability the loss of this checkpoint is associated with the mutational inactivation of a human homologue of the yeast BUB1 gene
-
-
?
ATP + a protein
ADP + a phosphoprotein
the enzyme is required for function of the spindle assembly checkpoint
-
-
?
ATP + a protein
ADP + a phosphoprotein
-
cell cycle-dependent expression, Bub1b has a putative destruction box that can target proteins for degradation by proteosomes during mitosis
-
-
?
ATP + a protein
ADP + a phosphoprotein
-
hBUBR1 may regulate multiple functions that include the kinetochore and the spindle midzone
-
-
?
ATP + a protein
ADP + a phosphoprotein
-
hBub1 is an important component of the spindle checkpoint pathway. hBub1 expression is restricted to proliferating cells and appears to be involved in regulating cell cycle progression
-
-
?
ATP + a protein
ADP + a phosphoprotein
-
Bub1 is required for binding Bub3
-
-
?
ATP + a protein
ADP + a phosphoprotein
-
huCdc7 may regulate processes of DNA replication by modulating MCM functions
-
-
?
ATP + a protein
ADP + a phosphoprotein
-
HsCdc7 may phosphorylate critical substrates that regulate the G1/S phase transition and/or DNA replication
-
-
?
ATP + AKAP450
ADP + phospho-AKAP450
-
wild-type substrate and GFP-tagged AKAP450 fragment containing the CK1delta-binding site
-
-
?
ATP + BAF155
ADP + phosphorylated BAF155
-
BAF155 is a hSWI/SNF protein that contains three Akt consensus sites, phosphorylation site analysis using recombinant full-length and truncated substrate versions, overview
-
-
?
ATP + beta-catenin
ADP + phosphorylated beta-catenin
-
-
by isozymes CK1delta and CK1epsilon
-
?
ATP + beta-catenin
ADP + phosphorylated beta-catenin
-
glycogen synthase kinase 3
-
-
?
ATP + beta-catenin
ADP + phosphorylated beta-catenin
-
phosphorylation at Ser45, priming GSK3beta phosphorylation
-
-
?
ATP + CDC25A
ADP + phospho-CDC25A
-
recombinantly expressed full-length wild-type CDC25A or CDC25A mutants S124A and S76A are used as substrates. STK38 phosphorylates wild-type CDC25A and mutant S124A at Ser76, it shows no activity with the S76A mutant
-
-
?
ATP + Cdc25A
ADP + phosphorylated Cdc25A
-
phosphorylation at S79 and S82 by isozyme CK1alpha
-
-
?
ATP + CREB
ADP + phosphorylated CREB
phosphorylation by TSSK5 at Ser133 stimulates the cAMP responsive element/cAMP responsive element binding protein CRE/CREB responsive pathway in recombinant HEK293 cells
-
-
?
ATP + CREB
ADP + phosphorylated CREB
i.e. cAMP responsive element binding protein, phosphorylation by TSSK5 at Ser133, no activity with CREB S133A mutant
-
-
?
ATP + Daxx
ADP + phosphorylated Daxx
-
Daxx is a protein acting in TGF-beta-induced JNK activation and in apoptosis
-
-
?
ATP + Daxx
ADP + phosphorylated Daxx
-
recombinant Daxx expressed as GST-fusion protein in Escherichia coli
-
-
?
ATP + geminin
ADP + phosphorylated geminin
-
a cell cycle regulatory protein
-
-
?
ATP + Gli protein
ADP + phosphorylated Gli protein
-
the Gli proteins are important in regulation of Hedgehog signaling, overview
-
-
?
ATP + glycogen synthase
ADP + phosphorylated glycogen synthase
-
glycogen synthase kinase 3
-
-
?
ATP + glycogen synthase
ADP + phosphorylated glycogen synthase
-
glycogen synthase kinase 3 is involved in the insulin signaling pathway regulating glycogen synthesis via glycogen synthase antagonizing insulin
-
-
?
ATP + glycogen synthase kinase 3
ADP + phosphorylated glycogen synthase kinase 3
-
PKB protein kinase
-
-
?
ATP + glycogen synthase kinase 3
ADP + phosphorylated glycogen synthase kinase 3
-
PKB protein kinase, phosphorylation at S21 and S9
-
-
?
ATP + granulocyte macrophage colony stimulating factor receptor
ADP + phospho-granulocyte macrophage colony stimulating factor receptor
-
-
-
?
ATP + granulocyte macrophage colony stimulating factor receptor
ADP + phospho-granulocyte macrophage colony stimulating factor receptor
Ser585 phosphorylation in the cytoplasmic domain
-
-
?
ATP + histone H1
ADP + phosphorylated histone H1
substrate from calf, substrate of SSTK
-
-
?
ATP + hypoxia-inducible factor-1
ADP + phosphorylated hypoxia-inducible factor-1
-
i.e. HIF-1, casein kinase 2 inhibits the activation of HIF-1 activity by phosphorylation and thereby stabilization of the protein, CK2 is involved in and influenced by hypoxia, overview
-
-
?
ATP + hypoxia-inducible factor-1
ADP + phosphorylated hypoxia-inducible factor-1
-
i.e. HIF-1
-
-
?
ATP + interleukin 3
ADP + phospho-interleukin-3
Ser585 phosphorylation in the cytoplasmic domain
-
-
?
ATP + myelin basic protein
ADP + phosphorylated myelin basic protein
-
-
-
?
ATP + myelin basic protein
ADP + phosphorylated myelin basic protein
-
-
-
?
ATP + phospholipase D
ADP + phosphorylated phospholipase D
-
CKII is involved in 4beta-phorbol 12-myristate 13-acetate-induced phospholipase D activation, of PLD1 or PLD2 activity as well as basal PLD activity
-
-
?
ATP + PKB protein kinase
ADP + phosphorylated PKB protein kinase
-
PDK1 kinase, phosphorylates Thr308 and Ser473, which is required for activation of PKB
-
-
?
ATP + PKB protein kinase
ADP + phosphorylated PKB protein kinase
-
PDK1 kinase
-
-
?
ATP + procaspase-2
ADP + phosphorylated procaspase-2
-
phosphorylation of procaspase-2 by CK2 prevents the activation of caspase activity by inhibiting the dimerization of procaspase-2, CK2 activity is involved in the direct regulation of the caspase-8 pathway, where it can control caspase-8 activity through the phosphorylation of ARC or by preventing the ability of caspase-8 to cleave its target Bid
-
-
?
ATP + protein
ADP + phosphoprotein
autophosphorylates exclusively serines within its COOH-terminal region in an intermolecular fashion
-
-
?
ATP + protein
ADP + phosphoprotein
-
minimum sequence required for efficient phosphorylation is Xaa-Xaa-Hyd-Xaa-Arg-Xaa-Xaa-Ser-Xaa-Xaa, where Hyd is a bulky hydrophobic residue (in decreasing order), Phe, Leu, Val, Ala, MAPKAP kinase-2 can not tolerate a proline residue at position n + 1
-
-
?
ATP + protein
ADP + phosphoprotein
the enzyme is an effector for Cdc42Hs and is implicated in the reorganization of the actin cytoskeleton and in the formation of filopodia
-
-
?
ATP + protein
ADP + phosphoprotein
PAK3 may be critical for human cognitive function
-
-
?
ATP + protein
ADP + phosphoprotein
-
the enzyme regulates the structure of the actin cytoskeleton in mammalian cells, and may serve as an effector for effector for Cdc42 and Rac1 in proll motility
-
-
?
ATP + protein
ADP + phosphoprotein
hPAK1 is a GTPase effector controlling a downstream MAP kinase pathway. PAK kinase plays a key part in linking extracellular signals from membrane components, such as receptor-associated G proteins and Rho-related GTPases, to nuclear responses, such as transcriptional activation
-
-
?
ATP + SC35
ADP + phosphorylated SC35
-
substrate prephosphorylated SC35, SC35 is a member of the SR family of serine/arginine-rich splicing factors
-
-
?
ATP + SC35
ADP + phosphorylated SC35
-
substrate prephosphorylated SC35, SC35 is a member of the SR family of serine/arginine-rich splicing factors, recombinant GSK-3beta
-
-
?
ATP + SF2/ASF
ADP + phosphorylated SF2/ASF
-
SF2/ASF is a human SR splicing factor, phosphorylation in the RS domain
-
-
?
ATP + SIV/17E-Fr Nef protein
ADP + phosphorylated SIV/17E-Fr Nef protein
-
phosphorylation at Ser12, the protein kinase CK2 associates with the Nef proteins from the Human immunodeficiency virus and the macrophage-tropic neurovirulent Simian immunodeficiency virus clone, SIV/17E-Fr, the Nef protein play important roles in viral disease progression
-
-
?
ATP + SIV/17E-Fr Nef protein
ADP + phosphorylated SIV/17E-Fr Nef protein
-
phosphorylation at Ser12, no or poor activity with SIV/17E-Fr Nef protein mutants S12P and D15A, respectively, in transfected 293T cells, Asp15 of the substrate is important for phosphorylation
-
-
?
ATP + Src protein
ADP + phosphorylated Src protein
recombinant Src expressed in HEK-293 cells, specific phosphorylation of Ser70, no activity with S70A Src mutant
-
-
?
ATP + tau protein
ADP + phosphorylated tau protein
-
tau in Alzheimer disease brain is highly phosphorylated and aggregates into paired helical filaments comprising characteristic neurofibrillary tangles, overview
-
-
?
ATP + tau protein
ADP + phosphorylated tau protein
-
determination of several phosphorylation sites, e.g. Ser258, Ser289, Ser262, and Ser356 within the microtubule-binding repeats or at Ser184 and Ser185 of the central region, for casein kinase I, casein kinase 2, and glycogen synthase kinase-3beta in insoluble tau, PHF-tau, extracted from Alzheimer brain and of tau from control healthy brain by mass spectrometry, overview
-
-
?
ATP + [tau-protein]
ADP + O-phospho -[tau-protein]
-
tau is primarily found in neurons, regulation of tau phosphorylation by GSK3beta via interaction with FRAT-1 and FRAT-2, i.e. frequently rearranged in advanced T-cell lymphoma proteins
-
-
?
ATP + [tau-protein]
ADP + O-phospho -[tau-protein]
-
phosphorylation of primed and unprimed sites by GSK3beta, wild-type and recombinant tau, recombinant GSK3beta S9A
-
-
?
ATP + [tau-protein]
ADP + O-phospho-[tau-protein]
-
-
-
-
?
ATP + [tau-protein]
ADP + O-phospho-[tau-protein]
-
phosphorylation of tau, especially at the primed epitope T231 negatively regulates tau-microtubule interactions, different effects of phosphorylation on primed T231 and unprimed S396/S404 epitopes of tau, overview
-
-
?
ATP + [tau-protein]
ADP + O-phospho-[tau-protein]
-
substrate of GSK3beta in brain
-
-
?
ATP + [tau-protein]
ADP + O-phospho-[tau-protein]
-
phosphorylation at the C-terminus, lower activity with C-terminally truncated tau D421 compared to the wild-type tau, the truncated tau protein forms sarcosyl-insoluble aggregates
-
-
?
ATP + [tau-protein]
ADP + O-phospho-[tau-protein]
-
substrate of GSK-3 in brain
-
-
?
additional information
?
-
-
LIMK may be involved in developmental or oncogenic processes through interactions with LIM-containing proteins
-
-
-
additional information
?
-
-
LIMK1 may be particularly relevant when explaining cognitive defects observed in WS patients
-
-
-
additional information
?
-
-
LIM-kinase 1 hemizygosity is implicated in impaired visuospatial constructive cognition
-
-
-
additional information
?
-
-
deranged transcriptional regulation of cell-volume-sensitive kinase hSGK in diabetic nephropathy
-
-
-
additional information
?
-
-
AKT1 gene is not a major contributor to susceptibility to type II diabetes mellitus in Ashkenazi Jews
-
-
-
additional information
?
-
K+-channel activation by all three isoforms of serum-dependent and glucocorticoid-dependent protein kinase SGK
-
-
-
additional information
?
-
-
the enzyme acts in concert with Akt to propagate the effects of PI3K activation within the nucleus and to mediate the biological outputs of PI3K signaling, including cell survival and cell cycle progression
-
-
-
additional information
?
-
-
transcript levels are strongly altered during anisotonic and isotonic cell volume changes
-
-
-
additional information
?
-
AKT2 may contribute to the pathogenesis of ovarian carcinomas
-
-
-
additional information
?
-
-
T-PK may have specialized functions in different areas of central nervous system. Alterations of this complex expression pattern can be responsible for the mental status impairment observed in myotonic dystrophy patients
-
-
-
additional information
?
-
-
enzyme may have a role in the development of mental symptoms in severe cases of myotonic dystrophy
-
-
-
additional information
?
-
mutations in the ribosomal S6 kinase (Rsk-2) gene are associated with Coffin-Lowry syndrome, an X-linked disorder characterized by facial dysmorphism, digit abnormalities and severe psychomotor retardation
-
-
-
additional information
?
-
-
mutations in the ribosomal S6 kinase (Rsk-2) gene are associated with Coffin-Lowry syndrome, an X-linked disorder characterized by facial dysmorphism, digit abnormalities and severe psychomotor retardation
-
-
-
additional information
?
-
-
mutations in the ribosomal S6 kinase (Rsk-2) gene are associated with Coffin-Lowry syndrome, an X-linked disorder characterized by facial dysmorphism, digit abnormalities and severe psychomotor retardation
-
-
-
additional information
?
-
ribosomal S6-kinase RSK4 is commonly deleted in patients with complex X-linked mental retardation, RSK4 plays a role in normal neuronal development. RSK4 is completely deleted in eight patients with the contiguous gene syndrome including MRX, partially deleted in a patient with DFN3 and present in patients with an Xq21 deletion and normal intellectual abilities
-
-
-
additional information
?
-
-
decreased expression of myotonin-protein kinase messenger RNA and protein in adult form of myotonic dystrophy
-
-
-
additional information
?
-
-
inherited defects in insulin-stimulated activation of muscle glycogen synthesis in patients with insulin-resistant NIDDM may be located further upstream of ISPK-1 in the insulin action cascade
-
-
-
additional information
?
-
-
Chk1 acts as an integrator for Atm and Atr signals and may be involved in monitoring the processing of meiotic recombination CHK1 gene is a candidate tumor suppressor gene
-
-
-
additional information
?
-
-
kinase functions downstream of ATM protein in the cellular response to DNA damage
-
-
-
additional information
?
-
-
in response to DNA damage, Chk1 phosphorylates and inhibits Cdc25C, thus preventing activation of the Cdc2-cyclin B complex and mitotic entry
-
-
-
additional information
?
-
-
in response to DNA damage and DNA replicational stress, Chk1 and Chk2 may phosphorylate Cdc25C to prevent entry into mitosis
-
-
-
additional information
?
-
-
heterozygous germ line mutations in hCHK2 occur in Li-Fraumeni syndrome, a highly penetrant familial cancer phenotype usually associated with inherited mutations in the TP53 gene. hCHK2 is a tumor suppressor gene conferring predisposition to sarcoma, breast cancer, and brain tumors
-
-
-
additional information
?
-
likely role for DCAMKL1 transmembrane protein in developing and adult brain, possibly in a pathway of cortical development
-
-
-
additional information
?
-
mutations of STK11 cause Peutz-Jeghers syndrome
-
-
-
additional information
?
-
-
Peutz-Jeghers syndrome is an autosomal-dominant disorder characterized by melanocytic macules of the lips, multiple gastrointestinal hamartomatous polyps and an increased risk for various neoplasms, including gastrointestinal cancer, germline mutations in STK11, probably in conjunction with acquired genetic defects of the second allele in somatic cells, cause the manifestations of PJ syndrome
-
-
-
additional information
?
-
-
Peutz-Jeghers syndrome is the first cancer-susceptibility syndrome to be identified that is due to inactivating mutations in a protein kinase, STK11
-
-
-
additional information
?
-
NH2-terminal region of hPRP4 may play regulatory roles under an unidentified signal transduction pathway through Clk1
-
-
-
additional information
?
-
-
calmodulin-binding region of titin can play a regulatory role for the enzyme
-
-
-
additional information
?
-
enzyme may function at an early step in phosphorylation events that are specific responses to some forms of chemical stress or extreme heat shock
-
-
-
additional information
?
-
enzyme may function at an early step in phosphorylation events that are specific responses to some forms of chemical stress or extreme heat shock
-
-
-
additional information
?
-
Nek2 protein is almost undetectable during G1 but accumulates progressively throughout S, reaching maximal levels in late G2, may function at the onset of mitosis
-
-
-
additional information
?
-
Nek2 protein is almost undetectable during G1 but accumulates progressively throughout S, reaching maximal levels in late G2, may function at the onset of mitosis
-
-
-
additional information
?
-
-
GSK-3 affects the tau-mRNA splicing of exon 10 via phosphorylation of the splicing factors of the serine/arginine-rich splicing factor SR family, e.g. SC35, leading to priming and dislocation of the splicing factor, aberrant tau splicing contributes to tauopathies including Alzheimer's disease, overview
-
-
-
additional information
?
-
-
GSK3beta works coordinatedly with PKA, EC 2.7.11.11, on tau phosphorylation
-
-
-
additional information
?
-
-
HIPK2 regulates transforming growth factor-beta-induced c-Jun NH(2)-terminal kinase activation and apoptosis in hepatoma cells, HIPK2 triggers promyelotic leukemia nuclear body disruption and release of Daxx
-
-
-
additional information
?
-
-
mechanism of Ca2+-mediated regulation of NDR protein kinase through autophosphorylation and phosphorylation by an upstream kinase
-
-
-
additional information
?
-
-
naturally occurring V717I mutation of the amyloid precursor protein APP in a CT100 fragment of organisms with Alzheimer's disease leads to augmented age-dependent tau phosphorylation, followed by increased activation status of mitogen-activated protein kinase family members, e.g. ERK1/2, p38, and c-Jun NH2-terminal kinase, compared to the wild-type organism, naturally occurring V337M mutation of tau protein of patients suffering Alzheimer's disease leads to age-dependent memory deficits
-
-
-
additional information
?
-
-
phosphorylated tau is important in cytoskeleton assembly
-
-
-
additional information
?
-
-
PKD2 regulation involving ligand-binding domains of the enzyme, isozyme PKD2 might play a role in the nucleus after activation by G protein-coupled receptors, overview, intracellular trafficking of PKD2, overview
-
-
-
additional information
?
-
-
regulation mechanism and biological function of PKN, PKNalpha is involved in insulin-induced actin cytoskeleton reorganization and cell adhesion, overview, PKNalpha is involved in vesicle transport in the endoplasmic reticulum, PKNalpha is cleaved by caspase-3 or related proteases in apoptotic Jurkat and U-937 cells contributing to signal transduction, PKN interacts with papillomaviral oncoproteins being involved in tumorigenesis, overview
-
-
-
additional information
?
-
serine/threonine protein kinase is SSTK essential for male fertility
-
-
-
additional information
?
-
-
the enzyme participates in Alzheimer's disease
-
-
-
additional information
?
-
-
CKII phosphorylates serine or threonine residues with an acidic amino acid in the +2 or +3 position
-
-
-
additional information
?
-
-
enzyme performs autophosphorylation, PKN binds several associated proteins via its ACC domain, i.e. RhoA, a small GTPase, which binds to the ACC domain of PKNalpha forming a catalytic active site
-
-
-
additional information
?
-
-
GSK-3alphabeta catalyzes tau phosphorylation in brain, but phosphorylation of glycogen synthase and other proteins, EC 2.7.11.1, in different tissues
-
-
-
additional information
?
-
-
GSK3beta catalyzes tau phosphorylation in brain, EC 2.7.11.26, but phosphorylation of glycogen synthase and other proteins in different tissues
-
-
-
additional information
?
-
-
GSK3beta catalyzes tau phosphorylation in brain, EC 2.7.11.26, but phosphorylation of glycogen synthase and other proteins in different tissues
-
-
-
additional information
?
-
-
GSK3beta catalyzes tau phosphorylation, EC 2.7.11.1, in brain, but phosphorylation of glycogen synthase and other proteins in different tissues
-
-
-
additional information
?
-
-
GSK3beta catalyzes tau phosphorylation, EC 2.7.11.26, in brain, but phosphorylation of glycogen synthase and other proteins in different tissues
-
-
-
additional information
?
-
-
NDR1 performs autophosphorylation at S281, T444, and T74 dependent on intracellular Ca2+
-
-
-
additional information
?
-
-
substrate ABC transporter protein structure, phosphorylation of the ABCA1 transporter reduces its flippase activity, overview
-
-
-
additional information
?
-
-
substrate specificity of PDK1, PDK1 binds the hydrophobic motif of substrates via its PIF pocket, GSK3 substrates need to bind tightly to the enzyme for phosphorylation
-
-
-
additional information
?
-
substrate specificity with diverse peptide substrates, overview, SSTK forms stable complexes with heat shock signate proteins HSP90-1beta, HSC70, and HSP70-1, which seems to be necessary for activity
-
-
-
additional information
?
-
-
CK2 is a highly conserved serine/threonine kinase involved in several intracellular pathways, which control, among others, cell cycle, proliferation, apoptosis and transformation, overview, protein kinase AKT interacts with CK2 subunits in vivo as well as in vitro enhancing AKT activity, overview
-
-
-
additional information
?
-
-
CK2 is involved in phosphorylation of a large portion of the proteome, overview, increased enzyme activity in associated with a number of pathological processes, including cancer, infectious diseases, neurodegeneration, and cardiovascular pathologies playing a global anti-apoptotic role, overview
-
-
-
additional information
?
-
-
CK2 phosphorylates about 300 different cellular proteins, ranging from transcription factors to proteins involved in chromatin structure and cell division, CK2 induces neoplastic growth when overexpressed
-
-
-
additional information
?
-
-
CK2 plays a role in the protection of cells from apoptosis via the regulation of tumor suppressor and oncogene activity and stability, e.g. in the NF-kappaB or the Wnt signaling pathways, molecular mechanisms, detailed overview, CK2 activity is linked to Her-2/neu oncogene, which is overexpressed in 30% of breast cancers, regulation of apoptotic machinery by CK2 and its anti-apoptotic effect, overview, role of CK2 in chromosomal DNA strand break repair and the maintenance of genomic integrity, mutational study, overview
-
-
-
additional information
?
-
-
high CK2 activity occurs in solid tumors due to growth-related functions and to suppression of cellular apoptosis, nuclear localization of domain CK2alpha is associated with high-grade tumors and a poor prognostic factor, overview
-
-
-
additional information
?
-
-
members of the hSWI/SNF chromatin remodeling complex associate with and are phosphorylated by protein kinase B/Akt, overview
-
-
-
additional information
?
-
-
multiple CKI family members play a role in both positively and negatively regulating Wnt and Hedgehog signaling, and the regulation of the stability of cytoplasmic beta-catenin, detailed overview, the partial degradation of Ci is promoted by phosphorylation and by a cytoplasmic complex, which includes Costal-2, a microtubule-binding protein, and Fused, a serine-threonine protein kinase
-
-
-
additional information
?
-
-
the enzyme inhibits NF-kappaB activity via interaction with the leucine-rich repeat domain of the Salmonella enterica serovar typhimurium-derived effector SspH1 in infected intestine-407 cells, overview
-
-
-
additional information
?
-
the enzyme is involved in the inflammation cascade in intestine and colon epithelium
-
-
-
additional information
?
-
-
CK2 contains a consensus sequence in which a carboxylic acid side chain at position n+3 relative to the target serine/threonine residue plays a crucial role for activity, CK2 shows a broad substrate specificity of diverse proteins
-
-
-
additional information
?
-
-
members of the hSWI/SNF chromatin remodeling complex associate with and are phosphorylated by protein kinase B/Akt, however, no Akt consensus sequences are found on BRG1, hBrm, BAF60, BAF57, or on INI1, overview
-
-
-
additional information
?
-
-
protein kinase AKT interacts with CK2 subunits in vivo as well as in vitro enhancing AKT activity, overview
-
-
-
additional information
?
-
-
the catalytic kinase domain, residues 561-942, of PKN1 is active with out the regulatory domain
-
-
-
additional information
?
-
-
the pleiotropic protein kinase CK2 possesses many protein interaction sites
-
-
-
additional information
?
-
-
enzyme binds both soluble inositol polyphosphates and inositol phospholipids
-
-
-
additional information
?
-
ULK3 shows autophosphorylation activity
-
-
-
additional information
?
-
phosphoinositide 3-kinase (PI3K) is a dual specificity kinase that is able to phosphorylate both lipid and protein substrates. In addition to their lipid kinase activity, all members of the class 1 PI3K family also possess intrinsic protein kinase activity
-
-
-
additional information
?
-
the enzyme is also active as lipid kinase generating phosphatidylinositol 1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate from 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
-
-
-
additional information
?
-
the PIKK family members phosphorylate proteins that regulate processes such as DNA repair, cell cycle progression, cellular senescence, and apoptosis
-
-
-
additional information
?
-
the PIKK family members phosphorylate proteins that regulate processes such as DNA repair, cell cycle progression, cellular senescence, and apoptosis
-
-
-
additional information
?
-
the PIKK family members phosphorylate proteins that regulate processes such as DNA repair, cell cycle progression, cellular senescence, and apoptosis
-
-
-
additional information
?
-
the PIKK family members phosphorylate proteins that regulate processes such as DNA repair, cell cycle progression, cellular senescence, and apoptosis
-
-
-
additional information
?
-
the enzyme does not phosphorylate Thr172, but suppresses its phosphorylation
-
-
-
additional information
?
-
the FATC domain reacts with membrane mimetics, titration analysis, overview
-
-
-
additional information
?
-
the FATC domain reacts with membrane mimetics, titration analysis, overview
-
-
-
additional information
?
-
the FATC domain reacts with membrane mimetics, titration analysis, overview
-
-
-
additional information
?
-
the FATC domain reacts with membrane mimetics, titration analysis, overview
-
-
-
additional information
?
-
the p110alpha catalytic subunit of PI3K can directly phosphorylate Ser585 of the GM-CSF and IL-3 receptors
-
-
-
additional information
?
-
-
TRPM4 phosphorylation site determination by peptide mapping
-
-
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
ATP + adenomatous polyposis coli protein
ADP + phosphorylated adenomatous polyposis coli protein
-
i.e. APC, APC is phosphorylated in vitro by CKIdelta and CKIepsilon
-
-
?
ATP + alpha-casein
ADP + phosphorylated alpha-casein
-
casein kinase 1alpha
-
-
?
ATP + AMP-activated protein kinase alpha1
ADP + phospho-AMP-activated protein kinase
P42336
phosphorylation of Ser485 at subunit alpha1 and of Ser491 at subunit alpha2
-
-
?
ATP + ataxin-3 protein
ADP + phosphorylated ataxin-3 protein
-
phosphorylation at serines 340 and 352
-
-
?
ATP + Cdk2 interacting protein
ADP + phosphorylated Cdk2 interacting protein
-
-
-
-
?
ATP + cell division cycle 7
ADP + phosphorylated cell division cycle 7
-
-
-
-
?
ATP + CREB
ADP + phosphorylated CREB
Q6SA08
phosphorylation by TSSK5 at Ser133 stimulates the cAMP responsive element/cAMP responsive element binding protein CRE/CREB responsive pathway in recombinant HEK293 cells
-
-
?
ATP + Daxx
ADP + phosphorylated Daxx
-
Daxx is a protein acting in TGF-beta-induced JNK activation and in apoptosis
-
-
?
ATP + geminin
ADP + phosphorylated geminin
-
a cell cycle regulatory protein
-
-
?
ATP + Gli protein
ADP + phosphorylated Gli protein
-
the Gli proteins are important in regulation of Hedgehog signaling, overview
-
-
?
ATP + glycogen synthase
ADP + phosphorylated glycogen synthase
-
glycogen synthase kinase 3 is involved in the insulin signaling pathway regulating glycogen synthesis via glycogen synthase antagonizing insulin
-
-
?
ATP + glycogen synthase kinase 3
ADP + phosphorylated glycogen synthase kinase 3
-
PKB protein kinase
-
-
?
ATP + granulocyte macrophage colony stimulating factor receptor
ADP + phospho-granulocyte macrophage colony stimulating factor receptor
P42336
-
-
-
?
ATP + hypoxia-inducible factor-1
ADP + phosphorylated hypoxia-inducible factor-1
-
i.e. HIF-1, casein kinase 2 inhibits the activation of HIF-1 activity by phosphorylation and thereby stabilization of the protein, CK2 is involved in and influenced by hypoxia, overview
-
-
?
ATP + M3-muscarnic receptor
ADP + phosphorylated M3-muscarnic receptor
-
-
-
-
?
ATP + non-structural protein 2
ADP + phosphorylated non-structural protein 2
-
-
-
-
?
ATP + OTUB1
ADP + phospho-OTUB1
-
OTUB1 is a tumor domain protease, phosphorylation at Ser16, in GSDSEGVN
-
-
?
ATP + OTUB1 protein
ADP + phosphorylated OTUB1 protein
-
phosphorylation at serine 16
-
-
?
ATP + OTUD5 protein
ADP + phosphorylated OTUD5 protein
-
phosphorylation at serine 177
-
-
?
ATP + peptide LRRKtide
ADP + phosphorylated peptide LRRKtide
-
high activity towards the peptidic substrate LRRKtide
-
-
?
ATP + phospholipase D
ADP + phosphorylated phospholipase D
-
CKII is involved in 4beta-phorbol 12-myristate 13-acetate-induced phospholipase D activation, of PLD1 or PLD2 activity as well as basal PLD activity
-
-
?
ATP + PKB protein kinase
ADP + phosphorylated PKB protein kinase
-
PDK1 kinase, phosphorylates Thr308 and Ser473, which is required for activation of PKB
-
-
?
ATP + procaspase-2
ADP + phosphorylated procaspase-2
-
phosphorylation of procaspase-2 by CK2 prevents the activation of caspase activity by inhibiting the dimerization of procaspase-2, CK2 activity is involved in the direct regulation of the caspase-8 pathway, where it can control caspase-8 activity through the phosphorylation of ARC or by preventing the ability of caspase-8 to cleave its target Bid
-
-
?
ATP + protein
ADP + protein tyrosine phosphate
P53667
phosphorylates and inactivates the actin binding/depolymerizing factor cofilin and induces actin cytoskeletal changes
-
-
?
ATP + SC35
ADP + phosphorylated SC35
-
substrate prephosphorylated SC35, SC35 is a member of the SR family of serine/arginine-rich splicing factors
-
-
?
ATP + SIV/17E-Fr Nef protein
ADP + phosphorylated SIV/17E-Fr Nef protein
-
phosphorylation at Ser12, the protein kinase CK2 associates with the Nef proteins from the Human immunodeficiency virus and the macrophage-tropic neurovirulent Simian immunodeficiency virus clone, SIV/17E-Fr, the Nef protein play important roles in viral disease progression
-
-
?
ATP + SR protein
ADP + ?
Q9H2X6
enzyme plays a role as a co-repressor for homeodomain transcription factors
-
-
?
ATP + SSH1L protein
ADP + SSH1L phosphoprotein
-
PKD1 phosphorylates the SSH enzyme SSH1L at serine 978
-
-
?
ATP + tau protein
ADP + phosphorylated tau protein
-
tau in Alzheimer disease brain is highly phosphorylated and aggregates into paired helical filaments comprising characteristic neurofibrillary tangles, overview
-
-
?
ATP + TRPM4
ADP + phospho-TRPM4
-
i.e. transient receptor potential melastatin-like 4, phosphorylation at Ser839
-
-
?
ATP + TRPM4 protein
ADP + phosphorylated TRPM4 protein
-
phosphorylation at serine 839
-
-
?
ATP + [tau-protein]
ADP + O-phospho -[tau-protein]
-
tau is primarily found in neurons, regulation of tau phosphorylation by GSK3beta via interaction with FRAT-1 and FRAT-2, i.e. frequently rearranged in advanced T-cell lymphoma proteins
-
-
?
ATP + a protein
ADP + a phosphoprotein
-
in some cancers displaying chromosomal instability the loss of this checkpoint is associated with the mutational inactivation of a human homologue of the yeast BUB1 gene
-
-
?
ATP + a protein
ADP + a phosphoprotein
O43683
the enzyme is required for function of the spindle assembly checkpoint
-
-
?
ATP + a protein
ADP + a phosphoprotein
-
cell cycle-dependent expression, Bub1b has a putative destruction box that can target proteins for degradation by proteosomes during mitosis
-
-
?
ATP + a protein
ADP + a phosphoprotein
-
hBUBR1 may regulate multiple functions that include the kinetochore and the spindle midzone
-
-
?
ATP + a protein
ADP + a phosphoprotein
-
hBub1 is an important component of the spindle checkpoint pathway. hBub1 expression is restricted to proliferating cells and appears to be involved in regulating cell cycle progression
-
-
?
ATP + a protein
ADP + a phosphoprotein
-
Bub1 is required for binding Bub3
-
-
?
ATP + a protein
ADP + a phosphoprotein
-
huCdc7 may regulate processes of DNA replication by modulating MCM functions
-
-
?
ATP + a protein
ADP + a phosphoprotein
-
HsCdc7 may phosphorylate critical substrates that regulate the G1/S phase transition and/or DNA replication
-
-
?
ATP + beta-catenin
ADP + phosphorylated beta-catenin
-
glycogen synthase kinase 3
-
-
?
ATP + beta-catenin
ADP + phosphorylated beta-catenin
-
phosphorylation at Ser45, priming GSK3beta phosphorylation
-
-
?
ATP + protein
ADP + phosphoprotein
O96013
the enzyme is an effector for Cdc42Hs and is implicated in the reorganization of the actin cytoskeleton and in the formation of filopodia
-
-
?
ATP + protein
ADP + phosphoprotein
O75914
PAK3 may be critical for human cognitive function
-
-
?
ATP + protein
ADP + phosphoprotein
-
the enzyme regulates the structure of the actin cytoskeleton in mammalian cells, and may serve as an effector for effector for Cdc42 and Rac1 in proll motility
-
-
?
ATP + protein
ADP + phosphoprotein
Q13153
hPAK1 is a GTPase effector controlling a downstream MAP kinase pathway. PAK kinase plays a key part in linking extracellular signals from membrane components, such as receptor-associated G proteins and Rho-related GTPases, to nuclear responses, such as transcriptional activation
-
-
?
ATP + [tau-protein]
ADP + O-phospho-[tau-protein]
-
-
-
-
?
ATP + [tau-protein]
ADP + O-phospho-[tau-protein]
-
phosphorylation of tau, especially at the primed epitope T231 negatively regulates tau-microtubule interactions, different effects of phosphorylation on primed T231 and unprimed S396/S404 epitopes of tau, overview
-
-
?
additional information
?
-
-
LIMK may be involved in developmental or oncogenic processes through interactions with LIM-containing proteins
-
-
-
additional information
?
-
-
LIMK1 may be particularly relevant when explaining cognitive defects observed in WS patients
-
-
-
additional information
?
-
-
LIM-kinase 1 hemizygosity is implicated in impaired visuospatial constructive cognition
-
-
-
additional information
?
-
-
deranged transcriptional regulation of cell-volume-sensitive kinase hSGK in diabetic nephropathy
-
-
-
additional information
?
-
-
AKT1 gene is not a major contributor to susceptibility to type II diabetes mellitus in Ashkenazi Jews
-
-
-
additional information
?
-
O00141
K+-channel activation by all three isoforms of serum-dependent and glucocorticoid-dependent protein kinase SGK
-
-
-
additional information
?
-
-
the enzyme acts in concert with Akt to propagate the effects of PI3K activation within the nucleus and to mediate the biological outputs of PI3K signaling, including cell survival and cell cycle progression
-
-
-
additional information
?
-
-
transcript levels are strongly altered during anisotonic and isotonic cell volume changes
-
-
-
additional information
?
-
P31751
AKT2 may contribute to the pathogenesis of ovarian carcinomas
-
-
-
additional information
?
-
-
T-PK may have specialized functions in different areas of central nervous system. Alterations of this complex expression pattern can be responsible for the mental status impairment observed in myotonic dystrophy patients
-
-
-
additional information
?
-
-
enzyme may have a role in the development of mental symptoms in severe cases of myotonic dystrophy
-
-
-
additional information
?
-
P51812
mutations in the ribosomal S6 kinase (Rsk-2) gene are associated with Coffin-Lowry syndrome, an X-linked disorder characterized by facial dysmorphism, digit abnormalities and severe psychomotor retardation
-
-
-
additional information
?
-
-
mutations in the ribosomal S6 kinase (Rsk-2) gene are associated with Coffin-Lowry syndrome, an X-linked disorder characterized by facial dysmorphism, digit abnormalities and severe psychomotor retardation
-
-
-
additional information
?
-
-
mutations in the ribosomal S6 kinase (Rsk-2) gene are associated with Coffin-Lowry syndrome, an X-linked disorder characterized by facial dysmorphism, digit abnormalities and severe psychomotor retardation
-
-
-
additional information
?
-
Q9UK32
ribosomal S6-kinase RSK4 is commonly deleted in patients with complex X-linked mental retardation, RSK4 plays a role in normal neuronal development. RSK4 is completely deleted in eight patients with the contiguous gene syndrome including MRX, partially deleted in a patient with DFN3 and present in patients with an Xq21 deletion and normal intellectual abilities
-
-
-
additional information
?
-
-
decreased expression of myotonin-protein kinase messenger RNA and protein in adult form of myotonic dystrophy
-
-
-
additional information
?
-
-
inherited defects in insulin-stimulated activation of muscle glycogen synthesis in patients with insulin-resistant NIDDM may be located further upstream of ISPK-1 in the insulin action cascade
-
-
-
additional information
?
-
-
Chk1 acts as an integrator for Atm and Atr signals and may be involved in monitoring the processing of meiotic recombination CHK1 gene is a candidate tumor suppressor gene
-
-
-
additional information
?
-
-
kinase functions downstream of ATM protein in the cellular response to DNA damage
-
-
-
additional information
?
-
-
in response to DNA damage, Chk1 phosphorylates and inhibits Cdc25C, thus preventing activation of the Cdc2-cyclin B complex and mitotic entry
-
-
-
additional information
?
-
-
in response to DNA damage and DNA replicational stress, Chk1 and Chk2 may phosphorylate Cdc25C to prevent entry into mitosis
-
-
-
additional information
?
-
-
heterozygous germ line mutations in hCHK2 occur in Li-Fraumeni syndrome, a highly penetrant familial cancer phenotype usually associated with inherited mutations in the TP53 gene. hCHK2 is a tumor suppressor gene conferring predisposition to sarcoma, breast cancer, and brain tumors
-
-
-
additional information
?
-
O15075
likely role for DCAMKL1 transmembrane protein in developing and adult brain, possibly in a pathway of cortical development
-
-
-
additional information
?
-
Q15831
mutations of STK11 cause Peutz-Jeghers syndrome
-
-
-
additional information
?
-
-
Peutz-Jeghers syndrome is an autosomal-dominant disorder characterized by melanocytic macules of the lips, multiple gastrointestinal hamartomatous polyps and an increased risk for various neoplasms, including gastrointestinal cancer, germline mutations in STK11, probably in conjunction with acquired genetic defects of the second allele in somatic cells, cause the manifestations of PJ syndrome
-
-
-
additional information
?
-
-
Peutz-Jeghers syndrome is the first cancer-susceptibility syndrome to be identified that is due to inactivating mutations in a protein kinase, STK11
-
-
-
additional information
?
-
Q13523
NH2-terminal region of hPRP4 may play regulatory roles under an unidentified signal transduction pathway through Clk1
-
-
-
additional information
?
-
-
calmodulin-binding region of titin can play a regulatory role for the enzyme
-
-
-
additional information
?
-
Q13043
enzyme may function at an early step in phosphorylation events that are specific responses to some forms of chemical stress or extreme heat shock
-
-
-
additional information
?
-
Q13188
enzyme may function at an early step in phosphorylation events that are specific responses to some forms of chemical stress or extreme heat shock
-
-
-
additional information
?
-
P51955
Nek2 protein is almost undetectable during G1 but accumulates progressively throughout S, reaching maximal levels in late G2, may function at the onset of mitosis
-
-
-
additional information
?
-
P51956
Nek2 protein is almost undetectable during G1 but accumulates progressively throughout S, reaching maximal levels in late G2, may function at the onset of mitosis
-
-
-
additional information
?
-
-
GSK-3 affects the tau-mRNA splicing of exon 10 via phosphorylation of the splicing factors of the serine/arginine-rich splicing factor SR family, e.g. SC35, leading to priming and dislocation of the splicing factor, aberrant tau splicing contributes to tauopathies including Alzheimer's disease, overview
-
-
-
additional information
?
-
-
GSK3beta works coordinatedly with PKA, EC 2.7.11.11, on tau phosphorylation
-
-
-
additional information
?
-
-
HIPK2 regulates transforming growth factor-beta-induced c-Jun NH(2)-terminal kinase activation and apoptosis in hepatoma cells, HIPK2 triggers promyelotic leukemia nuclear body disruption and release of Daxx
-
-
-
additional information
?
-
-
mechanism of Ca2+-mediated regulation of NDR protein kinase through autophosphorylation and phosphorylation by an upstream kinase
-
-
-
additional information
?
-
-
naturally occurring V717I mutation of the amyloid precursor protein APP in a CT100 fragment of organisms with Alzheimer's disease leads to augmented age-dependent tau phosphorylation, followed by increased activation status of mitogen-activated protein kinase family members, e.g. ERK1/2, p38, and c-Jun NH2-terminal kinase, compared to the wild-type organism, naturally occurring V337M mutation of tau protein of patients suffering Alzheimer's disease leads to age-dependent memory deficits
-
-
-
additional information
?
-
-
phosphorylated tau is important in cytoskeleton assembly
-
-
-
additional information
?
-
-
PKD2 regulation involving ligand-binding domains of the enzyme, isozyme PKD2 might play a role in the nucleus after activation by G protein-coupled receptors, overview, intracellular trafficking of PKD2, overview
-
-
-
additional information
?
-
-
regulation mechanism and biological function of PKN, PKNalpha is involved in insulin-induced actin cytoskeleton reorganization and cell adhesion, overview, PKNalpha is involved in vesicle transport in the endoplasmic reticulum, PKNalpha is cleaved by caspase-3 or related proteases in apoptotic Jurkat and U-937 cells contributing to signal transduction, PKN interacts with papillomaviral oncoproteins being involved in tumorigenesis, overview
-
-
-
additional information
?
-
Q9BXA6
serine/threonine protein kinase is SSTK essential for male fertility
-
-
-
additional information
?
-
-
the enzyme participates in Alzheimer's disease
-
-
-
additional information
?
-
-
CK2 is a highly conserved serine/threonine kinase involved in several intracellular pathways, which control, among others, cell cycle, proliferation, apoptosis and transformation, overview, protein kinase AKT interacts with CK2 subunits in vivo as well as in vitro enhancing AKT activity, overview
-
-
-
additional information
?
-
-
CK2 is involved in phosphorylation of a large portion of the proteome, overview, increased enzyme activity in associated with a number of pathological processes, including cancer, infectious diseases, neurodegeneration, and cardiovascular pathologies playing a global anti-apoptotic role, overview
-
-
-
additional information
?
-
-
CK2 phosphorylates about 300 different cellular proteins, ranging from transcription factors to proteins involved in chromatin structure and cell division, CK2 induces neoplastic growth when overexpressed
-
-
-
additional information
?
-
-
CK2 plays a role in the protection of cells from apoptosis via the regulation of tumor suppressor and oncogene activity and stability, e.g. in the NF-kappaB or the Wnt signaling pathways, molecular mechanisms, detailed overview, CK2 activity is linked to Her-2/neu oncogene, which is overexpressed in 30% of breast cancers, regulation of apoptotic machinery by CK2 and its anti-apoptotic effect, overview, role of CK2 in chromosomal DNA strand break repair and the maintenance of genomic integrity, mutational study, overview
-
-
-
additional information
?
-
-
high CK2 activity occurs in solid tumors due to growth-related functions and to suppression of cellular apoptosis, nuclear localization of domain CK2alpha is associated with high-grade tumors and a poor prognostic factor, overview
-
-
-
additional information
?
-
-
members of the hSWI/SNF chromatin remodeling complex associate with and are phosphorylated by protein kinase B/Akt, overview
-
-
-
additional information
?
-
-
multiple CKI family members play a role in both positively and negatively regulating Wnt and Hedgehog signaling, and the regulation of the stability of cytoplasmic beta-catenin, detailed overview, the partial degradation of Ci is promoted by phosphorylation and by a cytoplasmic complex, which includes Costal-2, a microtubule-binding protein, and Fused, a serine-threonine protein kinase
-
-
-
additional information
?
-
-
the enzyme inhibits NF-kappaB activity via interaction with the leucine-rich repeat domain of the Salmonella enterica serovar typhimurium-derived effector SspH1 in infected intestine-407 cells, overview
-
-
-
additional information
?
-
Q6E0B2
the enzyme is involved in the inflammation cascade in intestine and colon epithelium
-
-
-
additional information
?
-
-
enzyme binds both soluble inositol polyphosphates and inositol phospholipids
-
-
-
additional information
?
-
P42336
phosphoinositide 3-kinase (PI3K) is a dual specificity kinase that is able to phosphorylate both lipid and protein substrates. In addition to their lipid kinase activity, all members of the class 1 PI3K family also possess intrinsic protein kinase activity
-
-
-
additional information
?
-
P48736
the enzyme is also active as lipid kinase generating phosphatidylinositol 1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate from 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
-
-
-
additional information
?
-
P78527
the PIKK family members phosphorylate proteins that regulate processes such as DNA repair, cell cycle progression, cellular senescence, and apoptosis
-
-
-
additional information
?
-
Q13315
the PIKK family members phosphorylate proteins that regulate processes such as DNA repair, cell cycle progression, cellular senescence, and apoptosis
-
-
-
additional information
?
-
Q13535
the PIKK family members phosphorylate proteins that regulate processes such as DNA repair, cell cycle progression, cellular senescence, and apoptosis
-
-
-
additional information
?
-
Q96Q15
the PIKK family members phosphorylate proteins that regulate processes such as DNA repair, cell cycle progression, cellular senescence, and apoptosis
-
-
-
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COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
ATP
-
-
660909, 660948, 660951, 661422, 661900, 662053, 662134, 662175, 662260, 662261, 662313, 662388, 662674, 662737, 662817, 662855, 662857, 662912, 664864, 672409, 672431, 672994, 673856, 674068, 674847, 676261, 677245, 722198, 722389, 722795, 723080, 737612, 738021, 738583, 738673, 739390, 742249, 742890, 743270, 743408, 743837
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Ca2+
Mg2+
Mn2+
Zn2+
-
bound to the zinc finger core at residues 105-147 and coordinated by Cys109, Cys114, Cys137 ans Cys140, of the beta subunit dimer
Ca2+
-
autophosphorylation activity is repressed upon addition of Ca2+/calmodulin
Mg2+
-
-
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INHIBITORS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(5Z)-5-(1H-pyrrolo[2,3-b]pyridin-3-ylmethylidene)-2-thioxoimidazolidin-4-one
-
-
(S)-2-(2-aminopyrimidiny-4-yl)-7-(2-fluoroethyl)-1,5,6,7-tetrahydropyrrolo[3,2-c]pyridinione
-
-
1-(beta-D-2'-deoxyribofuranosyl)-4,5,6,7-tetrabromo-1H-benzimidazole
-
TDB, a cell-permeable selective inhibitor of CK2, inhibts the phosphorylation of OTUB1 at Ser16. In addition to CK2, TDB inhibits 3 other kinases, namely PIM1, CLK2 and DYRK1A, but none of these kinases phosphorylates OTUB1 in vitro
-
2-chloro-N-(4-(5-fluoro-2-(4-hydroxyphenylamino)pyrimidin-4-ylamino)phenyl)benzamide
-
3-{3-[4-(1-Methyl-1H-indol-3-yl)-2,5-dioxo-2,5-dihydro-1H-pyrrol-3-yl]-1H-indol-1-yl}propyl carbamimidothioate
-
-
4-(2-(4-(2-(4-acetylpiperazin-1-yl)-2-oxoethyl)phenylamino)-5-fluoropyrimidin-4-ylamino)-N-(2-chlorophenyl)benzamide
-
4-hydroxy-trans-2-nonenal
-
i.e. 4-HNE, binds to the enzyme at Lys197 and inhibits its activity by 69% by inhibiting its posttranslational phosphorylation. 4-HNE binding has no effect on the association of LKB1 with its adaptor proteins, sterile-20-related adaptor and mouse protein 25
7,9-dimethyl-8-(prop-2-en-1-yl)pyrido[3',2':4,5]thieno[3,2-d]pyrimidin-4-amine
-
-
Baicalin
-
one of the major compounds in the Chinese medical herb Scutellaria baicalensis, reduces enzyme expression and activity in badder cancer cells T24
FAALS
-
five amino-acid peptide inhibitor that is directed toward a noncatalytic binding pocket and which disrupts the cdk2/cyklin E complex
idelalisib
5-fluoro-3-phenyl-2-[(1S)-1-(9H-purin-6-ylamino)propyl]quinazolin-4(3H)-one, a PI3Kdelta inhibitor used to treat hematological malignancies. The inhibitior idelalisib is selective, noncovalent, reversible, and ATP-competitive, The compound binds reversibly and noncovalently to the p110delta subunit of the kinase, analysis of binding interactions that confer the potency and selectivity of idelalisib, overview. Idelalisib is a propeller-shaped inhibitor
indirubin-3'-monoxime
-
inhibition of AMPK, GSK3beta, S6K1, PKBalpha, PDK1, MAPKAP-K2
LAALS
-
five amino-acid peptide inhibitor that is directed toward a noncatalytic binding pocket and which disrupts the cdk2/cyklin E complex
lithium
-
after inhibition of GSK-3 in cortical neurons, the splicing factor SC35 is nuclearly redistributed and enriched in nuclear speckles and colocalizes with the kinase
N-(2-chlorophenyl)-4-(2-(4-(2-(4-ethylpiperazin-1-yl)-2-oxoethyl)phenylamino)-5-fluoropyrimidin-4-ylamino)benzamide
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N-(2-chlorophenyl)-4-(5-fluoro-2-(4-hydroxyphenylamino)pyrimidin-4-ylamino)benzamide
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N-cyclopropyl-4-(5-fluoro-2-(4-hydroxyphenylamino)pyrimidin-4-ylamino)benzamide
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N-ethyl-3-[[4-(4-methylpiperazin-1-yl)benzoyl]amino]-3a,6a-dihydro-1H-thieno[3,2-c]pyrazole-5-carboxamide
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N-[2-(4-fluorophenyl)ethyl]-5-[2-[(methylsulfonyl)amino]pyrimidin-4-yl]thiophene-2-carboxamide
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purvalanol
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inhibition of AMPK, slight inhibition of GSK3beta and S6K1, PKBalpha
TAACS
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five amino-acid peptide inhibitor that is directed toward a noncatalytic binding pocket and which disrupts the cdk2/cyklin E complex
TAALD
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five amino-acid peptide inhibitor that is directed toward a noncatalytic binding pocket and which disrupts the cdk2/cyklin E complex
TAALE
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five amino-acid peptide inhibitor that is directed toward a noncatalytic binding pocket and which disrupts the cdk2/cyklin E complex
enzastaurin
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activation-related phosphorylation of Y216/Y276 is dramatically decreased following exposure to enzastaurin whereas the inhibitory phosphorylation of S21 is significantly up-regulated in glioma cells. GSK3 inhibition results in glioma cell death and reduced tumorigenicity
additional information
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no inhibition of most serine/threonine kinases by roscovitine
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additional information
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GSK3 phosphorylation and inhibition by PKB protein kinase at S21 and S9
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additional information
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PKN possesses an autoinhibitory site at the C-terminal C2 domain, which also binds activating arachidonic acid
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additional information
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phosphorylation of GSK3beta at S9 inhibits the enzyme
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additional information
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the pleckstrin homology PH domain is a negative regulator of PKD2