Information on EC 2.7.11.18 - myosin-light-chain kinase

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The expected taxonomic range for this enzyme is: Eukaryota

EC NUMBER
COMMENTARY hide
2.7.11.18
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RECOMMENDED NAME
GeneOntology No.
myosin-light-chain kinase
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
ATP + [myosin light chain] = ADP + [myosin light chain] phosphate
show the reaction diagram
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
phospho group transfer
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SYSTEMATIC NAME
IUBMB Comments
ATP:[myosin light chain] O-phosphotransferase
Requires Ca2+ and calmodulin for activity. The 20-kDa light chain from smooth muscle myosin is phosphorylated more rapidly than any other acceptor, but light chains from other myosins and myosin itself can act as acceptors, but more slowly.
CAS REGISTRY NUMBER
COMMENTARY hide
51845-53-5
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ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
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Manually annotated by BRENDA team
cardiac/ventricular isozyme cardiac-MLCK encoded by gene MLCK3, and smooth muscle isozyme encoded by gene MLCK2
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Manually annotated by BRENDA team
strain Ax-3
SwissProt
Manually annotated by BRENDA team
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Manually annotated by BRENDA team
horseshoe crab
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Manually annotated by BRENDA team
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Manually annotated by BRENDA team
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Manually annotated by BRENDA team
Mus musculus C57BL/6
C57BL/6 mice
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Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
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MLCK-deficient mice lack bronchial constrictions in normal and asthmatic airways, while the asthmatic inflammation response is not affected
physiological function
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
ATP + 20kDa myosin light chain
ADP + 20kDa myosin light chain phosphate
show the reaction diagram
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phosphorylation occurs at Ser-19 and Thr-18
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-
?
ATP + BpaKKRAARATSNVFA
ADP + ?
show the reaction diagram
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Bpa is the photoreactive amino acid p-benzoylphenylalanine
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-
?
ATP + H-KKRAARATSNVFA-NH2
ADP + ?
show the reaction diagram
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peptide substrate
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?
ATP + kemptamide
ADP + ?
show the reaction diagram
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-
-
-
?
ATP + kemptamide
ADP + kemptamide phosphate
show the reaction diagram
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i.e. peptide KKRPQRATSNVFS-NH2, activated enzyme
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-
?
ATP + KKRAARATSNVFA
ADP + ?
show the reaction diagram
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-
-
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?
ATP + light chain myosin II
ADP + phosphorylated light chain myosin II
show the reaction diagram
ATP + Lys-Lys-Arg-Ala-Ala-Arg-Ala-Thr-Ser-Asn-Val-Phe-Ala
ADP + ?
show the reaction diagram
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-
-
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?
ATP + Lys-Lys-Arg-Pro-Gln-Arg-Ala-Thr-Ser-Asn-Val-Phe-Ser
ADP + ?
show the reaction diagram
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-
-
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?
ATP + myosin II
ADP + myosin II phosphate
show the reaction diagram
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from Dictyostelium discoideum, activated enzyme
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?
ATP + myosin IIB
ADP + phosphorylated myosin IIB
show the reaction diagram
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-
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?
ATP + myosin light chain
ADP + myosin light chain phosphate
show the reaction diagram
ATP + myosin light chain
ADP + phosphorylated myosin light chain
show the reaction diagram
ATP + myosin light chain 2
ADP + myosin light chain 2 phosphate
show the reaction diagram
ATP + myosin regulatory light chain
?
show the reaction diagram
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?
ATP + myosin regulatory light chain
ADP + myosin regulatory light chain phosphate
show the reaction diagram
ATP + myosin regulatory light chain
ADP + phosphorylated myosin regulatory light chain
show the reaction diagram
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?
ATP + myosin-II regulatory light chain
ADP + myosin-II regulatory light chain phosphate
show the reaction diagram
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?
ATP + obscurin
ADP + obscurin phosphate
show the reaction diagram
ATP + protein
ADP + phosphoprotein
show the reaction diagram
ATP + telokin
ADP + ?
show the reaction diagram
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telokin may modulate enzyme activity in vivo
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?
ATP + TRPC5 channel
ADP + phosphorylated TRPC5 channel
show the reaction diagram
Ca2+/calmodulin-dependent myosin light chain kinase is essential for activation of plasma membrane TRPC5 channels, responsible for Ca2+ influx, from Drosophila melanogaster expressed in HEK-293 cells, phosphorylation sites are Ser698, Ser775, and Thr700, mutational analysis
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?
ATP + [myosin II light chain]
ADP + [myosin II lihght chain] phosphate
show the reaction diagram
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from Dictyostelium discoideum, activated enzyme
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?
ATP + [myosin II regulatory light chain]
ADP + [myosin II regulatory light chain] phosphate
show the reaction diagram
ATP + [myosin light chain 2a]
ADP + [myosin light chain 2a] phosphate
show the reaction diagram
ATP + [myosin light chain]
ADP + [myosin light chain] phosphate
show the reaction diagram
additional information
?
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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 + light chain myosin II
ADP + phosphorylated light chain myosin II
show the reaction diagram
ATP + myosin IIB
ADP + phosphorylated myosin IIB
show the reaction diagram
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?
ATP + myosin light chain
ADP + myosin light chain phosphate
show the reaction diagram
ATP + myosin light chain
ADP + phosphorylated myosin light chain
show the reaction diagram
ATP + myosin light chain 2
ADP + myosin light chain 2 phosphate
show the reaction diagram
Q6PDN3
MLCK is involved in sarcomere organization, cardiac MLCK promotes sarcomere organization and increases cardiomyocyte contractility, overview
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?
ATP + myosin regulatory light chain
ADP + phosphorylated myosin regulatory light chain
show the reaction diagram
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?
ATP + obscurin
ADP + obscurin phosphate
show the reaction diagram
ATP + [myosin II regulatory light chain]
ADP + [myosin II regulatory light chain] phosphate
show the reaction diagram
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involved in many cellular cytoskeletal functions
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?
ATP + [myosin light chain 2a]
ADP + [myosin light chain 2a] phosphate
show the reaction diagram
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MLC phosphorylation plays a regulatory role in inotropic response to alpha1-adrenergic stimulation in the heart, enzyme inhibition causes heart failure in ventricular trabeculae
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?
ATP + [myosin light chain]
ADP + [myosin light chain] phosphate
show the reaction diagram
additional information
?
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COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
Calmodulin
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Calcium
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calcium-binding protein
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
(+)-catechin
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IC50: 0.44 mM
(-)-epicatechin
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IC50: 0.32 mM
1,12-diaminododecane
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IC50: 0.063 mM
1,4-diaminoanthraquinone
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IC50: 0.018 mM
1-hexadecylpyridinium bromide
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IC50: 0.049 mM
11-(3-chloro-6-iminopyridazin-1(6H)-yl)-N-(6-phenylpyridazin-3-yl)undecanamide
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highly specific inhibitor, competitive to ATP binding
2,2'-Dihydroxychalcone
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3',4',5'-tri-O-methyltricetin
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3',4'-dihydroxyflavone
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IC50: 0.262 mM
3,3',4'-trihydroxyflavone
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IC50: 0.001 mM
5,4'-dihydroxyflavone
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IC50: 0.024 mM
5,7-dihydroxyflavone
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IC50: 0.043 mM
7,8,3',4'-tetrahydroxyflavone
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IC50: 0.02 mM
7-O-methylapigenin
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acylcarnitin
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weak
AKKLSKDRMAAYMARRK
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synthetic peptide, analog of inhibitory region of myosin light chain kinase
AKKLSKDRMKKYMA
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synthetic peptide, analog of inhibitory region of myosin light chain kinase
AKKLSKDRMKKYMAAAA
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synthetic peptide, analog of inhibitory region of myosin light chain kinase
AKKLSKDRMKKYMARR
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synthetic peptide, analog of inhibitory region of myosin light chain kinase
AKKLSKDRMKKYMARRK
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synthetic peptide, analog of inhibitory region of myosin light chain kinase
AKKLSKDRMKKYMARRKWQKTG
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synthetic peptide, analog of inhibitory region of myosin light chain kinase
alizarin
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IC50: 0.014 mM
alkylamine
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long and straight chain, most effective with chain length C-13 to C-18
alkyltrimethylammonium halide
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amiloride
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anthraflavic acid
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IC50: 0.037 mM
anthrarufin
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apigenin
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IC50: 0.023 mM
arachidonic acid
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ARRKWQKTGHAVRAIGRLSS
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ATP
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free form, strong, not in the presence of excess Mg2+
blebbistatin
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complete inhibition at 0.1 mM
Ca2+
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at higher free concentrations, 0.4-3 mM, independent of Mg2+ or pH-value
Calmodulin-binding protein from bovine cardiac muscle
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cAMP-dependent protein kinase
Carbachol
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increases Ca2+ concentration, MLCK activation and regulatory light chain phosphorylation
chalcone
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chrysazine
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IC50: 0.02 mM
chrysophanic acid
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cytasters
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low inhibition
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D-Sphingosine
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IC50: 0.006 mM
decylamine
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IC50: 0.2 mM
dihydroapigenin
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IC50: 0.17 mM
dihydrofisetin
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IC50: 0.18 mM
dihydroluteolin
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dihydroquercetin
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IC50: 0.08 mM
dihydrosphingosine
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erythro- and threo-dihydrosphingosine, IC50: 0.008 mM
Dimethyldioctadecylammonium bromide
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IC50: 0.008 mM
dioctylamine
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IC50: 0.055 mM
dodecylamine
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IC50: 0.083 mM
dodecyltrimethylammonium bromide
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IC50: 0.078 mM
emodin
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IC50: 0.008 mM
fisetin
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IC50: 0.005 mM
galangin
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IC50: 0.02 mM
gossypol
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H1152
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low inhibition
hesperidin
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hexadecylamine
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IC50: 0.016 mM
Hexadecyltrimethylammonium bromide
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IC50: 0.011 mM
human arrest defective-1
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human arrest defective-1 is a bona fide regulator of MLCK, human arrest defective-1 associates with an IgG motif of MLCK and acetylates the Lys-608 residue in this motif and by so doing deactivates MLCK
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Increasing ionic strength
isoliquiritigenin
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kaempferid
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IC50: 0.008 mM
kaempferol
KDRMKKYMARR
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synthetic peptide, analog of inhibitory region of myosin light chain kinase
KKRAARATS-NH2
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i.e. KKRAARATS amide
KT5926
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i.e. (8R,9S,11S)-(-)-9-hydroxy-9-methoxycarbonyl-8-methyl-14-n-propoxy-2,3,9,10-tetrahydro-8,11-epoxy,1H,8H,11H-2,7beta,11alpha-triazadeibenzo[a,g]cycloocta[cde]triden-1-one, specific inhibitor
lauroylcholine iodide
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IC50: 0.12 mM
linoleic acid
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LSKDRMKKYMARRKWQK
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synthetic peptide, analog of inhibitory region of myosin light chain kinase
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luteolin
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IC50: 0.026 mM
merocyanine dye (C16)
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IC50: 0.040 mM
merocyanine dye (CH3)
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mitoxanthrone
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IC50: 0.002 mM
MLCK pepitde
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complete inhibition
morin
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IC50: 0.028 mM
MS-347a
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from Aspergillus sp. KY52178, structurally related to sydowinin B, irreversible, inhibition of calmodulin-dependent and independent activity, IC50: 0.0092 mM
myricetin
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IC50: 0.006 mM
myristoylcarnitine chloride
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myristoylcholine iodide
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IC50: 0.02 mM