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Information on EC 2.7.11.18 - myosin-light-chain kinase and Organism(s) Gallus gallus and UniProt Accession P11799
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2.7.11.18 myosin-light-chain kinaseIUBMB Comments
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.
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Word Map
- 2.7.11.18
-
contractile
- actin
- junction
- artery
- rho
- pkc
- agonist
- gizzard
- cytoskeletal
- actomyosin
-
tension
- occludin
-
rock
-
calmodulin-binding
-
actin-activated
-
isometric
-
rho-associated
- mlc20
-
paracellular
-
ca2+-independent
-
actin-myosin
-
rho-kinase
- wortmannin
-
zonula
- mypt1
-
cam-binding
-
actin-binding
-
cam-dependent
- trifluoperazine
- caldesmon
-
myofilament
-
hyperpermeability
-
thrombin-induced
-
thiophosphorylation
- mg2+-atpase
- calyculin
-
pseudosubstrate
- blebbistatin
- idella
-
diphosphorylation
- calponin
-
cross-bridge
- meromyosin
- medicine
-
mgatpase
-
myosin-binding
-
monoxime
-
n-6-aminohexyl-5-chloro-1-naphthalenesulfonamide
-
calmodulin-activated
-
superprecipitation
- cak
The taxonomic range for the selected organisms is: Gallus gallus
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
Synonyms
mlck, myosin light chain kinase, myosin light-chain kinase, mlc kinase, smooth muscle myosin light chain kinase, smmlck, nmmlck, myosin kinase, cmlck, skmlck, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
myosin light chain kinase
-
myosin light chain kinase, smooth muscle and non-muscle isozymes
-
calcium/calmodulin-dependent myosin light chain kinase
-
-
-
-
kinase, myosin light-chain (phosphorylating)
-
-
-
-
myosin kinase
-
-
-
-
myosin light chain protein kinase
-
-
-
-
myosin light-chain kinase
smooth-muscle-myosin-light-chain kinase
-
-
-
-
myosin light-chain kinase
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
phospho group transfer
-
-
-
-
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
51845-53-5
-
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 + [non-muscle heavy meromyosin IIB]
ADP + [non-muscle heavy meromyosin IIB] phosphate
-
-
-
?
ATP + [non-muscle regulatory light chain]
ADP + [non-muscle regulatory light chain] phosphate
-
-
-
?
ATP + [smooth muscle heavy meromyosin]
ADP + [smooth muscle heavy meromyosin] phosphate
-
-
-
?
ATP + [smooth muscle regulatory light chain]
ADP + [smooth muscle regulatory light chain] phosphate
-
-
-
?
ATP + myosin light chain
ADP + myosin light chain phosphate
activated MLCK then phosphorylates the regulatory myosin light chains, triggering cross-bridge cycling and contraction, myosin light chain phosphorylation is increased under these conditions, suggesting that contraction would be potentiated by ablation of AMPK
-
-
?
ATP + myosin light chain
ADP + phosphorylated myosin light chain
-
-
-
?
ATP + myosin light chain
ADP + phosphorylated myosin light chain
-
-
-
?
ATP + myosin light chain
ADP + phosphorylated myosin light chain
-
-
-
?
ATP + [myosin light chain]
ADP + [myosin light chain] phosphate
non-muscle myosin II
-
-
?
ATP + [myosin light chain]
ADP + [myosin light chain] phosphate
non-muscle myosin II and preferred substrate smooth muscle myosin II
-
-
?
ATP + [myosin light chain]
ADP + [myosin light chain] phosphate
phosphorylation of myosin on Ser19 of the regulatory light chain. Non-muscle myosin II regulatory light chain and preferred substrate smooth muscle myosin II regulatory light chain
-
-
?
ATP + [myosin light chain]
ADP + [myosin light chain] phosphate
smooth muscle myosin regulatory light chain phosphorylation at Ser19
-
-
?
ATP + myosin light chain
ADP + myosin light chain phosphate
-
-
-
-
?
ATP + myosin light chain
ADP + myosin light chain phosphate
-
acceptor substrates are myosin light chains of smooth muscle myosin
-
?
ATP + myosin light chain
ADP + myosin light chain phosphate
-
acceptor substrates are myosin light chains of smooth muscle myosin
-
?
ATP + myosin light chain
ADP + myosin light chain phosphate
-
no substrates are myosin heavy chain and phosvitin
-
-
?
ATP + myosin light chain
ADP + myosin light chain phosphate
-
acceptor substrates are myosin light chains of skeletal muscle
-
?
ATP + myosin light chain
ADP + myosin light chain phosphate
-
acceptor substrates are myosin light chains of skeletal muscle
-
-
?
ATP + myosin light chain
ADP + myosin light chain phosphate
-
acceptor substrates are myosin light chains of cardiac muscle
-
?
ATP + myosin light chain
ADP + myosin light chain phosphate
-
no substrate is histone 2-A
-
?
ATP + myosin light chain
ADP + myosin light chain phosphate
-
acceptor substrates are myosin light chains of non-muscle myosin
-
-
?
ATP + myosin light chain
ADP + myosin light chain phosphate
-
not specific for 22 kDa and 15 kDa light chain
-
-
?
ATP + myosin light chain
ADP + myosin light chain phosphate
-
no substrate is casein
-
?
ATP + myosin light chain
ADP + myosin light chain phosphate
-
no substrate is casein
-
?
ATP + myosin light chain
ADP + myosin light chain phosphate
-
no substrate is casein
-
-
?
ATP + myosin light chain
ADP + myosin light chain phosphate
-
no substrate is troponin
-
-
?
ATP + myosin light chain
ADP + myosin light chain phosphate
-
highly specific for regulatory or P-light-chain
-
?
ATP + myosin light chain
ADP + myosin light chain phosphate
-
1 mol phosphate per mol light chain in skeletal muscle
-
?
ATP + myosin light chain
ADP + myosin light chain phosphate
-
no substrate is phosphorylase kinase
-
-
?
ATP + myosin light chain
ADP + myosin light chain phosphate
-
acceptor substrates are myosin light chains of smooth muscle
-
?
ATP + myosin light chain
ADP + myosin light chain phosphate
-
acceptor substrates are myosin light chains of smooth muscle
-
?
ATP + myosin light chain
ADP + myosin light chain phosphate
-
acceptor substrates are myosin light chains of smooth muscle
-
?
ATP + myosin light chain
ADP + myosin light chain phosphate
-
acceptor substrates are myosin light chains of smooth muscle
-
?
ATP + myosin light chain
ADP + myosin light chain phosphate
-
acceptor substrates are myosin light chains of smooth muscle
-
?
ATP + myosin light chain
ADP + myosin light chain phosphate
-
acceptor substrates are myosin light chains of smooth muscle
-
-
?
ATP + myosin light chain
ADP + myosin light chain phosphate
-
specific for 20 kDa light chain
-
?
ATP + myosin light chain
ADP + myosin light chain phosphate
-
no substrate is histone V-S
-
?
ATP + myosin light chain
ADP + myosin light chain phosphate
-
no substrate is phosphorylase b
-
?
ATP + myosin light chain
ADP + myosin light chain phosphate
-
no substrate is phosphorylase b
-
?
ATP + myosin light chain
ADP + myosin light chain phosphate
-
no substrate is phosphorylase b
-
-
?
ATP + myosin light chain
ADP + myosin light chain phosphate
-
kinase from skeletal muscle with broader specificity than smooth muscle kinase
-
-
?
ATP + myosin light chain
ADP + myosin light chain phosphate
-
involved in muscle contractility and motility of non-muscle cells
-
-
?
ATP + myosin light chain
ADP + myosin light chain phosphate
-
event in initiation of smooth-muscle contraction
-
-
?
ATP + myosin light chain
ADP + myosin light chain phosphate
-
inhibition of actin-myosin ineraction
-
-
?
ATP + myosin light chain
ADP + myosin light chain phosphate
-
the enzyme has effects on the actin-myosin interaction in vitro, regulation of actin-myosin interaction by MLCK through its non-kinase activity, overview
-
-
?
ATP + myosin light chain
ADP + myosin light chain phosphate
-
20 kDa regulatory light chain of smooth muscle
-
-
?
additional information
?
-
MLCK is a substrate of AMP-activated protein kinase, AMPK
-
-
?
additional information
?
-
-
MLCK is a substrate of AMP-activated protein kinase, AMPK
-
-
?
additional information
?
-
non-muscle myosin and smooth muscle myosin are the only known substrates of MLCK in vivo
-
-
?
additional information
?
-
MLCK has a 2fold higher kcat for both smooth muscle myosin II substrates compared with non-muscle myosin IIB substrates, whereas Km values are very similar. Myosin light chain kinase has a 1.6fold and 1.5fold higher specificity (kcat/Km) for smooth versus non-muscle-free regulatory light chain and heavy meromyosin, respectively, suggesting that differences in specificity are dictated by regulatory light chain sequences. Three residues, Glu70, Gly71, and Ser74, are found to be surface exposed in the N-terminal half of the regulatory light chain, consistent with their importance in substrate recognition. Substrate recognition and specificity, overview
-
-
?
additional information
?
-
static substrate binding structure of streptavidin-tagged enzyme, overview
-
-
?
additional information
?
-
-
skeletal, gizzard smooth and cardiac enzymes perform intramolecular autophosphorylation in the absence of acceptor substrate
-
-
?
additional information
?
-
-
the enzyme is a potential cytoskeleton integrator through its unique N-terminal domain, the enzyme binds tubulin and actin, and is involved in microtubule/microfilament association
-
-
?
additional information
?
-
-
the enzyme is a key regulator of various forms of cell motility involving actin and myosin II
-
-
?
additional information
?
-
-
actin-myosin interaction of smooth muscle could be activated by the non-kinase activity of MLCK, a mechanism that is quite independent of MLC20 phosphorylation, role of non-kinase activity of myosin light-chain kinase in regulating smooth muscle contraction, overview. MLCK phosphorylated at Ser828 stimulates the ATPase activity of unphosphorylated myosin more effectively than the control MLCK
-
-
?
additional information
?
-
-
the enzyme also exerts non-kinase activity on myosin motor and myosin ATPase activities
-
-
?
NATURAL SUBSTRATE
NATURAL 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 + myosin light chain
ADP + myosin light chain phosphate
activated MLCK then phosphorylates the regulatory myosin light chains, triggering cross-bridge cycling and contraction, myosin light chain phosphorylation is increased under these conditions, suggesting that contraction would be potentiated by ablation of AMPK
-
-
?
ATP + myosin light chain
ADP + phosphorylated myosin light chain
-
-
-
?
ATP + myosin light chain
ADP + phosphorylated myosin light chain
-
-
-
?
ATP + myosin light chain
ADP + phosphorylated myosin light chain
-
-
-
?
ATP + [myosin light chain]
ADP + [myosin light chain] phosphate
non-muscle myosin II
-
-
?
ATP + [myosin light chain]
ADP + [myosin light chain] phosphate
non-muscle myosin II and preferred substrate smooth muscle myosin II
-
-
?
ATP + myosin light chain
ADP + myosin light chain phosphate
-
-
-
-
?
ATP + myosin light chain
ADP + myosin light chain phosphate
-
involved in muscle contractility and motility of non-muscle cells
-
-
?
ATP + myosin light chain
ADP + myosin light chain phosphate
-
event in initiation of smooth-muscle contraction
-
-
?
ATP + myosin light chain
ADP + myosin light chain phosphate
-
inhibition of actin-myosin ineraction
-
-
?
additional information
?
-
MLCK is a substrate of AMP-activated protein kinase, AMPK
-
-
?
additional information
?
-
-
MLCK is a substrate of AMP-activated protein kinase, AMPK
-
-
?
additional information
?
-
non-muscle myosin and smooth muscle myosin are the only known substrates of MLCK in vivo
-
-
?
additional information
?
-
-
the enzyme is a potential cytoskeleton integrator through its unique N-terminal domain, the enzyme binds tubulin and actin, and is involved in microtubule/microfilament association
-
-
?
additional information
?
-
-
the enzyme is a key regulator of various forms of cell motility involving actin and myosin II
-
-
?
additional information
?
-
-
actin-myosin interaction of smooth muscle could be activated by the non-kinase activity of MLCK, a mechanism that is quite independent of MLC20 phosphorylation, role of non-kinase activity of myosin light-chain kinase in regulating smooth muscle contraction, overview. MLCK phosphorylated at Ser828 stimulates the ATPase activity of unphosphorylated myosin more effectively than the control MLCK
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Calmodulin
-
requirement
Calmodulin
-
trypsin or chymotrypsin digested smooth muscle enzyme is independent of Ca2+/calmodulin
Calmodulin
-
calmodulin in presence of Ca2+ abolishes the inhibition of actin-myosin interaction
Calmodulin
-
optimal ratio of enzyme to calmodulin for telokin phosphorylation is 1:4
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Mg2+
Ca2+
Ca2+
-
-
Ca2+
-
Ca2+ in presence of calmodulin abolishes the inhibition of actin-myosin interaction
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
alkylamine
-
long and straight chain, most effective with chain length C-13 to C-18
MS-347a
-
from Aspergillus sp. KY52178, structurally related to sydowinin B, irreversible, inhibition of calmodulin-dependent and independent activity, IC50: 0.0092 mM
Wortmannin
-
i.e. MS-54, IC50: 0.0019 mM, irreversible, highly selective, kinetics, high concentrations of ATP protect
additional information
autoregulatory domain extends from Asn780 to Arg808. The peptide Leu774 to Ser787 does not inhibit smMLCK, peptides of similar or shorter length from the pseudosubstrate region, Ser787 to Val807, are potent inhibitors
-
additional information
-
autoregulatory domain extends from Asn780 to Arg808. The peptide Leu774 to Ser787 does not inhibit smMLCK, peptides of similar or shorter length from the pseudosubstrate region, Ser787 to Val807, are potent inhibitors
-
additional information
MLCK is inhibited as the ionic strength increases
-
additional information
phosphorylation at serine residues 140/149 by cAMP-dependent protein kinase (PKA) and Aurora B leads to a decrease in N27-157 binding to actin
-
additional information
-
no inhibition by epicatechin, pseudobabtisin, 4-dimethylaminobenzaldehyde
-
additional information
-
oxytoxin and phorbol ester do not affect the enzyme activity. Non-kinase, inhibitory activity of N-terminal, actin-binding domain of MLCK
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
methylcellulose
enhances the rate of MLCK-induced phosphorylation of smooth muscle myosin and MLCK-induced mechanical activation of smooth muscle myosin to move actin filaments
-
additional information
enzyme MLCK210 possesses actin binding regions both in the central part of the molecule and in its N-terminal tail domain
-
additional information
kinetics of myosin light chain kinase activation of smooth muscle myosin in an in vitro model system, overview. Actin has no activating effect on the enzyme activity
-
additional information
-
oxytoxin and phorbol ester do not affect the enzyme activity
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
additional information
kinetics of myosin light chain kinase activation of smooth muscle myosin in an in vitro model system, kinetic modelling, overview. The dissociation of MLCK from phosphorylated smooth muscle myosin is rate-limiting and that the rate of the phosphorylation step is faster than this dissociation rate. Association to smooth muscle myosin is much faster than to smooth muscle myosin. The probability of MLCK interacting with unphosphorylated versus smooth muscle myosin is 55-460 times greater
-
additional information
additional information
steady-state kinetic parameters of MLCK toward 4 different substrates: the 2-headed heavy meromyosin (HMM) soluble subfragments of both smooth muscle myosin II and non-muscle myosin IIB, each containing their respective smooth or non-muscle regulatory light chains, and the 2 types of free regulatory light chains. MLCK has an about 2fold higher kcat for both smooth muscle myosin II substrates compared with non-muscle myosin IIB substrates, whereas Km values are very similar
-
additional information
additional information
-
in the presence of wortmannin
-
additional information
additional information
-
kinetic constants for enzymes from various sources with different myosin light chains as substrates
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
additional information
steady-state kinetics: comparison of smooth muscle myosin II and non-muscle myosin IIB as substrates, overview. MLCK has an about 2fold higher kcat for both smooth muscle myosin II substrates compared with non-muscle myosin IIB substrates, whereas Km values are very similar
-
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
additional information
myosin light chain kinase has a 1.6fold and 1.5fold higher kcat/Km for smooth versus non-muscle-free regulatory light chain and heavy meromyosin, respectively
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.008
dihydrosphingosine
Gallus gallus
-
erythro- and threo-dihydrosphingosine, IC50: 0.008 mM
0.0092
MS-347a
Gallus gallus
-
from Aspergillus sp. KY52178, structurally related to sydowinin B, irreversible, inhibition of calmodulin-dependent and independent activity, IC50: 0.0092 mM
0.0019
Wortmannin
Gallus gallus
-
i.e. MS-54, IC50: 0.0019 mM, irreversible, highly selective, kinetics, high concentrations of ATP protect
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
SwissProt
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
from embryos, in myofibril precursors and sarcomeric Z-lines, co-localization with myosin IIB
additional information
-
-
640620, 640624, 640635, 640639, 640640, 640645, 640648, 640649, 640650, 640651, 640652, 640653, 640655, 708823
-
-
additional information
myosin light chain kinase is a ubiquitous Ca2+/calmodulin (CaM)-activated kinase found in smooth, cardiac, and skeletal muscle as well as in mammalian non-muscle cells
additional information
-
myosin light chain kinases in smooth muscle and non-muscle tissues are the same protein
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
additional information
-
subcellular localization study of MLCK in embryonic cardiomyocytes, overview
-
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
physiological function
malfunction
in knockout mice, the lack of MLCK-mediated phosphorylation of myosin in tracheal, bronchial, and gastrointestinal smooth muscle cannot be rescued by other kinases
malfunction
mutation S140D/S149D attenuates the phosphorylation at Ser140 and Ser149 by PKA and Aurora B kinases
physiological function
high molecular weight myosin light chain kinase is a multifunctional protein involved in myosin II activation and integration of cytoskeletal components in cells, phosphorylation regulates interaction of 210-kDa myosin light chain kinase N-terminal domain with actin cytoskeleton. Phosphorylation at serine residues 140/149 by cAMP-dependent protein kinase (PKA) and Aurora B leads to a decrease in N27-157 binding to actin. Enzyme-cytoskeleton interactions: in non-muscle cells, MLCK210 functions as a cytoskeleton integrator and motility organizer. MLCK210 resides on microfilament bundles via its central high affinity actin binding site, whereas both the N- and C-terminal tails of the molecule are engaged in reversible interaction with other cytoskeletal and motile components of the cell. While MLCK210 resides on actin filaments, its KRPdomain binds to soluble monomeric non-muscle myosin II and facilitates the presentation of myosin II to the catalytic core of the kinase. Phosphorylation of myosin II allows selfassembly of myosin filaments, thereby supporting localized actomyosin motility, modelling
physiological function
MLCK-induced phosphorylation of smooth muscle myosin and MLCK-induced mechanical activation of smooth muscle myosin to move actin filaments, likely by increasing the time the MLCK remains close to the surface-attached myosin
physiological function
phosphorylation of myosin on S19 of the regulatory light chain (also called LC20) activates myosin ATPase activity in the presence of actin, which is necessary and sufficient for muscle contraction. All smooth muscles express two forms of myosin II, SMM (most abundant in adult tissues; includes 4 alternatively spliced variants derived from a single SMM heavy chain gene: 1A, 1B, 2A, and 2B) and NMM (IIA, IIB, and IIC minor). The smooth muscle enzyme prefers the smooth muscle myosin II regulatory light chain to the non-muscle myosin II. Non-muscle myosin IIB may participate in a physiologically relevant pathway for force maintenance in smooth muscle
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). MYLK_CHICK
1906
0
210446
Swiss-Prot
other Location (Reliability: 5)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
-
different molecular weights may be due to high sensitivity to proteolysis during purification
additional information
-
relative masses of various animal skeletal muscle enzymes
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
-
multienzyme complex with smooth muscle myosin light chain phosphatase
additional information
-
skeletal muscle myosin light chain kinases from different species share more identity than skeletal muscle and smooth muscle myosin light chain kinases from the same species
additional information
-
skeletal muscle enzyme structure: overall asymmetric shape, globular head and tail region
additional information
-
different molecular weights may be due to high sensitivity to proteolysis during purification
additional information
-
MLCK-210 contains an additional actin-binding domain at the N-terminus
additional information
-
MLCK domain structure, a fusion protein consisting of the Nterminal actin-binding domain, the central catalytic domain, and the C-terminal myosin-binding domain
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
phosphoprotein
in vitro, the N-terminal actinbinding domain of MLCK210 is located within residues 27-157 and is phosphorylated by cAMP-dependent protein kinase (PKA) and Aurora B at serine residues 140/149 leading to a decrease in N27-157 binding to actin, leading role of the S149D mutation in attenuation of N27-157 binding to the cytoskeletal structures. In vitro phosphorylation and determination of phosphorylation sites, overview
phosphoprotein
-
protein kinase A phosphorylates MLCK in its regulatory domain at Ser815 and Ser828. The kinase activity of MLCK phosphorylated at Ser815 is reduced, whereas that of MLCK phosphorylated at Ser828 is not reduced
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
S140D/S149D
site-directed mutagenesis of MLCK, the mutation attenuates the phosphorylation at Ser140 and Ser149 by PKA and Aurora B kinases, overview
additional information
additional information
the kinase activity of biotinylated-MLCK is comparable to MLCK without biotinylation using the regulatory light chain as the substrate. Biotinylated-MLCK and biotinylated-MLCK with attached streptavidin tag are able to fully phosphorylate smooth muscle myosin regulatory light chain
additional information
-
deletion of DRFXXL motifs leads to a worse binding to actin filaments especially in the presence of Mg2+
additional information
-
downregulation of MLCK in cultured smooth muscle cells reveals that MLC20 phosphorylation is not obligatory for the smooth muscle to contract, overview
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
purified to homogeneity from a number of vertebrate muscles and partially purified from non-muscle tissues
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
domain organization of chicken gizzard myosin light chain kinase deduced from a cloned cDNA
recombinant expression of FLAG-tagged N27-157 wild-type or phospho-mutant S140A/S149A constructs in HeLa cells
expression of His6-tagged MLCK-210 nad His-tagged N452-MLCK in Escherichia coli, expression of GFP-tagged MLCK-210 and GFP-tagged N452-MLCK in CV-1 African green monkey kidney cells
-
transient expression as GFP fusion protein in A7r5, HeLa, NIH3T3 or COS-7 cells
-
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Collinge, M.; Matrisian, P.E.; Zimmer, W.E.; Shattuck, R.L.; Lukas, T.J.; Van Eldik, L.J.; Watterson, D.M.
Structure and expression of a calcium-binding protein gene contained within a calmodulin-regulated protein kinase gene
Mol. Cell. Biol.
12
2359-2371
1992
Gallus gallus (P11799), Gallus gallus
Guerriero, V.Jr.; Russo, M.A.; Olson, N.J.; Putkey, J.A.; Means, A.R.
Domain organization of chicken gizzard myosin light chain kinase deduced from a cloned cDNA
Biochemistry
25
8372-8381
1986
Gallus gallus (P11799), Gallus gallus
Olson, N.J.; Pearson, R.B.; Needleman, D.S.; Hurwitz, M.Y.; Kemp, B.E.; Means, A.R.
Regulatory and structural motifs of chicken gizzard myosin light chain kinase
Proc. Natl. Acad. Sci. USA
87
2284-2288
1990
Gallus gallus (P11799), Gallus gallus
Shoemaker, M.O.; Lau, W.; Shattuck, R.L.; Kwiatkowski, A.P.; Matrisian, P.E.; Guerra-Santos, L.; Wilson, E.; Lukas, T.J.; Van Eldik, L.J.; Watterson, D.M.
Use of DNA sequence and mutant analyses and antisense oligodeoxynucleotides to examine the molecular basis of nonmuscle myosin light chain kinase autoinhibition, calmodulin recognition, and activity
J. Cell Biol.
111
1107-1125
1990
Gallus gallus (P11799), Gallus gallus
Watterson, D.M.; Collinge, M.; Lukas, T.J.; Van Eldik, L.J.; Birukov, K.G.; Stepanova, O.V.; Shirinsky, V.P.
Multiple gene products are produced from a novel protein kinase transcription region
FEBS Lett.
373
217-220
1995
Gallus gallus (P11799)
Yoshikai, S.; Ikebe, M.
Molecular cloning of the chicken gizzard telokin gene and cDNA
Arch. Biochem. Biophys.
299
242-247
1992
Gallus gallus (P11799), Gallus gallus
Gallagher, P.J.; Herring, B.P.; Griffin, S.A.; Stull, J.T.
Molecular characterization of a mammalian smooth muscle myosin light chain kinase [published erratum appears in J Biol Chem 1992 May 5;267(13):9450]
J. Biol. Chem.
266
23936-23944
1991
Bos taurus, Gallus gallus, Oryctolagus cuniculus, Oryctolagus cuniculus (P29294), Rattus norvegicus
Walsh, M.P.; Hinkins, S.; Flink, I.L.; Hartshorne, D.J.
Bovine stomach myosin light chain kinase: purification, characterization, and comparison with the turkey gizzard enzyme
Biochemistry
21
6890-6896
1982
Bos taurus, Gallus gallus, Meleagris gallopavo
Yamazaki, K.; Itoh, K.; Sobue, K.; Mori, T.; Shibata, N.
Purification of caldesmon and myosin light chain (MLC) kinase from arterial smooth muscle: comparisons with gizzard caldesmon and MLC kinase
J. Biochem.
101
1-9
1987
Bos taurus, Gallus gallus
Jinsart, W.; Ternai, B.; Polya, G.M.
Inhibition of myosin light chain kinase, cAMP-dependent protein kinase, protein kinase C and of plant Ca(2+)-dependent protein kinase by anthraquinones
Biol. Chem. Hoppe-Seyler
373
903-910
1992
Gallus gallus
Nunnally, M.H.; Rybicki, S.B.; Stull, J.T.
Characterization of chicken skeletal muscle myosin light chain kinase. Evidence for muscle-specific isozymes
J. Biol. Chem.
260
1020-1026
1985
Gallus gallus, Oryctolagus cuniculus
Leachman, S.A.; Gallagher, P.J.; Herring, B.P.; McPhaul, M.J.; Stull, J.T.
Biochemical properties of chimeric skeletal and smooth muscle myosin light chain kinases
J. Biol. Chem.
267
4930-4938
1992
Gallus gallus
Bailin, G.
Structure and function of a calmodulin-dependent smooth muscle myosin light chain kinase
Experientia
40
1185-1188
1984
Bos taurus, Gallus gallus, Oryctolagus cuniculus, Meleagris gallopavo
Jinsart, W.; Ternai, B.; Polya, G.M.
Inhibition of wheat embryo calcium-dependent protein kinase and avian myosin light chain kinase by flavonoids and related compounds
Biol. Chem. Hoppe-Seyler
372
819-827
1991
Gallus gallus
Nakanishi, S.; Kakita, S.; Takahashi, I.; Kawahara, K.; Tsukada, E.; Sano, T.; Yamada, K.; Yoshida, M.; Kase, H.; Matsuda, Y.; Hashimoto, Y.; Nonomura, Y.
Wortmannin, a microbial product inhibitor of myosin light chain kinase
J. Biol. Chem.
267
2157-2163
1992
Gallus gallus
Nakanishi, S.; Ando, K.; Kawamoto, I.; Matsuda, Y.
MS-347a, a new inhibitor of myosin light chain kinase from Aspergillus sp. KY52178
J. Antibiot.
46
1775-1781
1989
Gallus gallus
-
Jinsart, W.; Ternai, B.; Polya, G.M.
Inhibition and activation of wheat embryo calcium-dependent protein kinase and inhibition of avian myosin light chain kinase by long chain aliphatic amphiphiles
Plant Sci.
78
165-175
1991
Gallus gallus
-
Stull, J.T.; Nunnally, M.H.; Michnoff, C.H in
Calmoduline-dependent protein kinases
The Enzymes, 3rd. Ed. (Boyer, P. D. , Krebs, E. G. , eds. )
17
113-166
1986
Bos taurus, Canis lupus familiaris, Cavia porcellus, Gallus gallus, Homo sapiens, Meleagris gallopavo, Rattus norvegicus
-
Fujita, K.; Ye, L.H.; Sato, M.; Okagaki, T.; Nagamachi, Y.; Kohama, K.
Myosin light chain kinase from skeletal muscle regulates an ATP-dependent interaction between actin and myosin by binding to actin
Mol. Cell. Biochem.
190
85-90
1999
Gallus gallus
Okagaki, T.; Ye, L.H.; Samizo, K.; Tanaka, T.; Kohama, K.
Inhibitory effect of the catalytic domain of myosin light chain kinase on actin-myosin interaction: insight into the mode of inhibition
J. Biochem.
125
1055-1060
1999
Gallus gallus
Okagaki, T.; Hayakawa, K.; Samizo, K.; Kohama, K.
Inhibition of the ATP-dependent interaction of actin and myosin by the catalytic domain of the myosin light chain kinase of smooth muscle: possible involvement in smooth muscle relaxation
J. Biochem.
125
619-626
1999
Gallus gallus
Hayakawa, K.; Okagaki, T.; Ye, L.H.; Samizo, K.; Higashi-Fujime, S.; Takagi, T.; Kohama, K.
Characterization of the myosin light chain kinase from smooth muscle as an actin-binding protein that assembles actin filaments in vitro
Biochim. Biophys. Acta
1450
12-24
1999
Gallus gallus
Sobieszek, A.; Andruchov, O.Y.; Nieznanski, K.
Kinase-related protein (telokin) is phosphorylated by smooth-muscle myosin light-chain kinase and modulates the kinase activity
Biochem. J.
328
425-430
1997
Gallus gallus
-
Edwards, R.A.; Walsh, M.P.; Sutherland, C.; Vogel, H.J.
Activation of calcineurin and smooth muscle myosin light chain kinase by Met-to-Leu mutants of calmodulin
Biochem. J.
331
149-152
1998
Gallus gallus
-
Sobieszek, A.; Borkowski, J.; Babiychuk, V.S.
Purification and characterization of a smooth muscle myosin light chain kinase-phosphatase complex
J. Biol. Chem.
272
7034-7041
1997
Gallus gallus
Van Lierop, J.E.; Wilson, D.P.; Davis, J.P.; Tikunova, S.; Sutherland, C.; Walsh, M.P.; Johnson, J.D.
Activation of smooth muscle myosin light chain kinase by calmodulin. Role of Lys30 and Gly40
J. Biol. Chem.
277
6550-6558
2002
Gallus gallus, Rattus norvegicus
Smith, L.; Parizi-Robinson, M.; Zhu, M.S.; Zhi, G.; Fukui, R.; Kamm, K.E.; Stull, J.T.
Properties of long myosin light chain kinase binding to F-actin in vitro and in vivo
J. Biol. Chem.
277
35597-35604
2002
Gallus gallus
Kudryashov, D.S.; Stepanova, O.V.; Vilitkevich, E.L.; Nikonenko, T.A.; Nadezhdina, E.S.; Shanina, N.A.; Lukas, T.J.; Van Eldik, L.J.; Watterson, D.M.; Shirinsky, V.P.
Myosin light chain kinase (210 kDa) is a potential cytoskeleton integrator through its unique N-terminal domain
Exp. Cell Res.
298
407-417
2004
Gallus gallus
Dudnakova, T.V.; Stepanova, O.V.; Dergilev, K.V.; Chadin, A.V.; Shekhonin, B.V.; Watterson, D.M.; Shirinsky, V.P.
Myosin light chain kinase colocalizes with nonmuscle myosin IIB in myofibril precursors and sarcomeric Z-lines of cardiomyocytes
Cell Motil. Cytoskeleton
63
375-383
2006
Gallus gallus, Homo sapiens
Nakamura, A.; Xie, C.; Zhang, Y.; Gao, Y.; Wang, H.H.; Ye, L.H.; Kishi, H.; Okagaki, T.; Yoshiyama, S.; Hayakawa, K.; Ishikawa, R.; Kohama, K.
Role of non-kinase activity of myosin light-chain kinase in regulating smooth muscle contraction, a review dedicated to Dr. Setsuro Ebashi
Biochem. Biophys. Res. Commun.
369
135-143
2008
Bos taurus, Gallus gallus
Horman, S.; Morel, N.; Vertommen, D.; Hussain, N.; Neumann, D.; Beauloye, C.; El Najjar, N.; Forcet, C.; Viollet, B.; Walsh, M.P.; Hue, L.; Rider, M.H.
AMP-activated protein kinase phosphorylates and desensitizes smooth muscle myosin light chain kinase
J. Biol. Chem.
283
18505-18512
2008
Mus musculus, Gallus gallus (P11799), Gallus gallus, Rattus norvegicus (P20689)
Xie, C.; Zhang, Y.; Wang, H.H.; Matsumoto, A.; Nakamura, A.; Ishikawa, R.; Yoshiyama, S.; Hayakawa, K.; Kohama, K.; Gao, Y.
Calcium regulation of non-kinase and kinase activities of recombinant myosin light-chain kinase and its mutants
IUBMB Life
61
1092-1098
2009
Gallus gallus, Bos taurus (Q28824)
Vilitkevich, E.L.; Khapchaev, A.Y.; Kudryashov, D.S.; Nikashin, A.V.; Schavocky, J.P.; Lukas, T.J.; Watterson, D.M.; Shirinsky, V.P.
Phosphorylation regulates interaction of 210-kDa myosin light chain kinase N-terminal domain with actin cytoskeleton
Biochemistry (Moscow)
80
1288-1297
2015
Gallus gallus (P11799)
Hong, F.; Facemyer, K.C.; Carter, M.S.; Jackson, d.e.l..R.; Haldeman, B.D.; Ruana, N.; Sutherland, C.; Walsh, M.P.; Cremo, C.R.; Baker, J.E.
Kinetics of myosin light chain kinase activation of smooth muscle myosin in an in vitro model system
Biochemistry
52
8489-8500
2013
Gallus gallus (P11799)
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