Information on EC 2.7.11.7 - myosin-heavy-chain kinase

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The expected taxonomic range for this enzyme is: Eukaryota

EC NUMBER
COMMENTARY
2.7.11.7
-
RECOMMENDED NAME
GeneOntology No.
myosin-heavy-chain kinase
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
ATP + [myosin heavy-chain] = ADP + [myosin heavy-chain] phosphate
show the reaction diagram
activation of the enzyme by autophosphorylation is necessary for full catalytic activity
-
ATP + [myosin heavy-chain] = ADP + [myosin heavy-chain] phosphate
show the reaction diagram
catalytic domain: amino acid residues 31-259
-, Q8MY12
ATP + [myosin heavy-chain] = ADP + [myosin heavy-chain] phosphate
show the reaction diagram
catalytic domain structure, modeling; residues Ser627, Thr631 and Thr632 are essential for catalytic activity
-
ATP + [myosin heavy-chain] = ADP + [myosin heavy-chain] phosphate
show the reaction diagram
major phosphorylation site: Ser8
Q869N2
ATP + [myosin heavy-chain] = ADP + [myosin heavy-chain] phosphate
show the reaction diagram
enzyme contains the C-terminal WD-domain, responsible for substrate binding, the catalytic domain, and the N-terminal coiled-coil translocation domain
-
ATP + [myosin heavy-chain] = ADP + [myosin heavy-chain] phosphate
show the reaction diagram
catalytic domain: amino acid residues 31-259
-
-
ATP + [myosin heavy-chain] = ADP + [myosin heavy-chain] phosphate
show the reaction diagram
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
phospho group transfer
-
-
-
-
SYSTEMATIC NAME
IUBMB Comments
ATP:[myosin heavy-chain] O-phosphotransferase
The enzyme from Dictyostelium sp. (slime moulds) brings about phosphorylation of the heavy chains of Dictyostelium myosin, inhibiting the actin-activated ATPase activity of the myosin. One threonine residue in each heavy chain acts as acceptor. While the enzyme from some species is activated by actin, in other cases Ca2+/calmodulin are required for activity.
SYNONYMS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
kinase (phosphorylating), myosin heavy chain
-
-
-
-
MHCK
Dictyostelium discoideum AX3
P34125
-
-
MHCK
Dictyostelium discoideum JH10
-
-
-
myosin heavy chain kinase
-
-
-
-
myosin heavy chain kinase A
-
-
myosin heavy chain kinase A
P42527
-
myosin heavy chain kinase B
P90648
-
myosin heavy chain kinase C
Q8MY12
-
myosin I heavy-chain kinase
-
-
-
-
myosin II heavy chain kinase
-
-
myosin II heavy chain kinase A
P42527
-
myosin II heavy chain kinase B
P90648
-
myosin II heavy chain kinases A
P42527
-
myosin II heavy chain kinases B
P90648
-
myosin II heavy-chain kinase
-
-
-
-
additional information
Q93107
member of the p21-activated kinase family
additional information
Q869N2
member of the p21-activated kinase family
CAS REGISTRY NUMBER
COMMENTARY
64763-54-8
-
ORGANISM
COMMENTARY
LITERATURE
SEQUENCE CODE
SEQUENCE DB
SOURCE
myosin II heavy chain kinase
-
-
Manually annotated by BRENDA team
purified myosin I heavy chain kinase
SwissProt
Manually annotated by BRENDA team
gene MHCK A, myosin II heavy chain kinase A
SwissProt
Manually annotated by BRENDA team
gene MHCK A; isozyme myosin II heavy chain kinase A; strain JH10
-
-
Manually annotated by BRENDA team
gene MHCK A; two heavy chain kinases: one in growth-phase cells and one in starved, developing cells
-
-
Manually annotated by BRENDA team
gene MHCK B, myosin II heavy chain kinase B
SwissProt
Manually annotated by BRENDA team
gene MHCK C, myosin II heavy chain kinase C
O76739
GenBank
Manually annotated by BRENDA team
gene MHCK, myosin heavy chain kinase
SwissProt
Manually annotated by BRENDA team
gene MHCK; strain AX3
SwissProt
Manually annotated by BRENDA team
gene MHKA or MHCKA, myosin heavy chain kinase A
SwissProt
Manually annotated by BRENDA team
gene MHKB or MHCKB, myosin heavy chain kinase B
SwissProt
Manually annotated by BRENDA team
isozyme MHCK A
SwissProt
Manually annotated by BRENDA team
isozyme MHCK A; isozyme MHCK A
SwissProt
Manually annotated by BRENDA team
isozyme myosin II heavy chain kinase A; strain Ax-3
-
-
Manually annotated by BRENDA team
myosin I heavy chain kinase
SwissProt
Manually annotated by BRENDA team
myosin I heavy chain kinase
SwissProt
Manually annotated by BRENDA team
myosin II heavy chain kinase C, gene mhckC; strain AX2
SwissProt
Manually annotated by BRENDA team
myosin II heavy chain kinase MHCK A
SwissProt
Manually annotated by BRENDA team
the 3 isozymes MHCK A, MHCK B, and MHCK C
-
-
Manually annotated by BRENDA team
two heavy chain kinases: one in growth-phase cells and one in starved, developing cells
-
-
Manually annotated by BRENDA team
Dictyostelium discoideum Ax-3
strain Ax-3
-
-
Manually annotated by BRENDA team
Dictyostelium discoideum AX3
strain AX3
SwissProt
Manually annotated by BRENDA team
Dictyostelium discoideum JH10
strain JH10
-
-
Manually annotated by BRENDA team
the Ca2+/calmodulin dependent heavy chain kinase has several properties in common with the family of type II calmodulin-dependent protein kinases; two myosin heavy-chain kinases: a Ca2+/calmodulin dependent and a Ca2+/calmodulin independent enzyme
-
-
Manually annotated by BRENDA team
two myosin heavy-chain kinases: a Ca2+/calmodulin dependent and a Ca2+/calmodulin independent enzyme
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
evolution
-
myosin II heavy chain kinase A is a member of the atypical alpha-kinase family
evolution
-
alpha-kinases transfer the gamma-phosphate of ATP to protein substrates through an aspartylphosphate intermediate
malfunction
P90648
removal of the N-rich region severely compromises MHC phosphorylation by the catalytic domain. Removal of both the N-rich and WD-repeat domains renders the catalytic domain barely able to phosphorylate MHC above detectable levels, whereas the truncation containing the N-rich region can still use MHC as a substrate, albeit at about 30% of that displayed by the full-length kinase. But the innate kinase activity of the catalytic domain is not lost upon removal of the N-rich region and/or the WD-repeat domain of MHCK-B since all three versions of MHCK-B phosphorylated MH-1 peptide to the same level
physiological function
P90648
heavy chain phosphorylation plays a central role in regulating myosin II bipolar filament assembly in Dictyostelium
physiological function
-
the enzyme phosphorylates sites in the myosin II tail that block filament assembly
physiological function
-
myosin II heavy chain kinase A, MHCK A, disrupts the assembly and cellular activity of bipolar filaments of myosin II by phosphorylating sites within its alpha-helical, coiled-coil tail
malfunction
-
the catalytic activity of A-CAT, the alpha-kinase domain of MHCKA comprising residues 552-841, is severely inhibited by the removal of a disordered C-terminal tail residues 806-841
additional information
P90648
mechanism for targeting myosin II heavy chain phosphorylation by myosin heavy chain kinase B, overview. An intrinsically unstructured, and asparagine-rich, region of a MHCK-B can mediate specific targeting of the kinase to phosphorylate myosin II heavy chain involving a direct binding interaction with myosin II filaments, while the the WD repeat domain is not absolutely required in MHCK-B substrate targeting, in contrast to isozyme MHCK-A. The N-rich region facilitates phosphorylation of MHC by binding directly to myosin II filaments
additional information
-
the phosphate-pocket functions as a positive allosteric binding site, the phosphorylated Thr825 activates alpha-kinase domain by providing a covalently tethered ligand for the phosphate-pocket, mechanism modeling
additional information
-
ADP is bound at the active site and invariant Asp766 at the active site is phosphorylated in the crysstallized MHCK A. The aspartylphosphate group is exposed to the solvent within an active-site pocket that might function as a docking site for substrates. Access to the aspartylphosphate is regulated by a conformational switch in a loop that binds to a Mg2+ ion, providing a mechanism that allows alpha-kinases to sense and respond to local changes in Mg2+ concentration. Access to the active-site pocket was regulated by a C-terminal glycine-rich loop that bound to Mg2+ and switched between two distinct conformations. The invariant Asp766 residue is located at the center rear of the active site where it interacted with phosphate, the alpha-phosphate of AMP, and Mg2+ in the active-site pocket
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
ATP + AKRVSMMR
ADP + AKRVS(-phosphate)MMR
show the reaction diagram
Q869N2
peptide derived from myosin I heavy chain kinase amino acid residues 4-11, exchange at position 4: Ser to Ala
phophorylation site is Ser8
?
ATP + caldesmon
ADP + caldesmon phosphate
show the reaction diagram
O76739, P42527, P90648
catalytic domain
-
-
?
ATP + casein
ADP + casein phosphate
show the reaction diagram
-
-
-
-
?
ATP + casein
ADP + casein phosphate
show the reaction diagram
-
no activity
-
-
-
ATP + casein
ADP + casein phosphate
show the reaction diagram
-
poor substrate
-
-
?
ATP + casein
ADP + casein phosphate
show the reaction diagram
O76739, P42527, P90648
catalytic domain, low activity
-
-
?
ATP + chicken gizzard myosin light chain
ADP + chicken gizzard myosin light chain phosphate
show the reaction diagram
-
no activity
-
-
-
ATP + chicken gizzard myosin light chain
ADP + chicken gizzard myosin light chain phosphate
show the reaction diagram
-
poor substrate
-
-
?
ATP + GRGRSSVYS
ADP + GRGRSS(-phosphate)VYS
show the reaction diagram
-
-
-
-
?
ATP + GRGRSSVYS
ADP + GRGRSS(-phosphate)VYS
show the reaction diagram
-
synthetic peptide with a sequence corresponding to the phosphorylation site of myosin IC
-
?
ATP + GRGRSSVYS
ADP + GRGRSS(-phosphate)VYS
show the reaction diagram
-
synthetic peptide with a sequence corresponding to the phosphorylation site of myosin IC
-
?
ATP + GRGRSSVYS
ADP + GRGRSS(-phosphate)VYS
show the reaction diagram
-
synthetic peptide with a sequence corresponding to the phosphorylation site of myosin IC
-
-
?
ATP + GRGRSSVYS
ADP + GRGRSS(-phosphate)VYS
show the reaction diagram
Q93107
synthetic peptide with a sequence corresponding to the phosphorylation site of myosin IC
-
-
?
ATP + GRGRSSVYS
ADP + GRGRSS(-phosphate)VYS
show the reaction diagram
-
synthetic peptide with a sequence corresponding to the phosphorylation site of myosin IC
-
-
?
ATP + GRSARVSTYA
ADP + GRSARVS(-phosphate)TYA
show the reaction diagram
Q869N2
peptide derived from Dictyostelium myosin ID
-
?
ATP + histone 2A
ADP + histone 2A phosphate
show the reaction diagram
-
-
-
-
?
ATP + histone 2A
ADP + histone 2A phosphate
show the reaction diagram
-
no activity
-
-
-
ATP + histone 2A
ADP + histone 2A phosphate
show the reaction diagram
-
low activity
-
-
?
ATP + MH1 peptide
ADP + MH1 peeptide phosphate
show the reaction diagram
P90648
-
-
-
?
ATP + myelin basic protein
ADP + myelin basic protein phosphate
show the reaction diagram
O76739, P42527, P90648
catalytic domain
-
-
?
ATP + myosin heavy chain
ADP + myosin heavy chain phosphate
show the reaction diagram
-
-
-
?
ATP + myosin heavy chain
ADP + myosin heavy chain phosphate
show the reaction diagram
-
-
-
?
ATP + myosin heavy chain
ADP + myosin heavy chain phosphate
show the reaction diagram
-
-
-
?
ATP + myosin heavy chain
ADP + myosin heavy chain phosphate
show the reaction diagram
-
substrate specificity
-
?
ATP + myosin heavy chain
ADP + myosin heavy chain phosphate
show the reaction diagram
-
phosphorylates threonine residues
-
?
ATP + myosin heavy chain
ADP + myosin heavy chain phosphate
show the reaction diagram
-
phosphorylates threonine residues, rabbit skeletal myosin heavy chains are phosphorylated, 0.7 mol phosphate per mol of heavy chain
-
?
ATP + myosin heavy chain
ADP + myosin heavy chain phosphate
show the reaction diagram
-
best substrate: chicken intestine brush border myosin
-
?
ATP + myosin heavy chain
ADP + myosin heavy chain phosphate
show the reaction diagram
-
best substrate: chicken intestine brush border myosin
-
?
ATP + myosin heavy chain
ADP + myosin heavy chain phosphate
show the reaction diagram
-
protamine is no substrate, no activity with myosins from gizzard, cardiac or skeletal muscle, but active with the isolated 20 kDa gizzard myosin light chain, substrate: bovine brain myosin
-
?
ATP + myosin heavy chain
ADP + myosin heavy chain phosphate
show the reaction diagram
-
specific for myosin heavy chains, no phosphorylation of light chains
-
?
ATP + myosin heavy chain
ADP + myosin heavy chain phosphate
show the reaction diagram
-
specific for myosin heavy chains, no phosphorylation of light chains
-
?
ATP + myosin heavy chain
ADP + myosin heavy chain phosphate
show the reaction diagram
-
specific for myosin heavy chains, no phosphorylation of light chains
-
?
ATP + myosin heavy chain kinase
ADP + myosin heavy chain kinase phosphate
show the reaction diagram
-
35 kDa trypsin fragment of the C-terminus of the maximally activated, phosphorylated enzyme is fully catalytically active and contains 2 thirds of the autophosphorylation sites of the native enzyme
-
?
ATP + myosin heavy chain kinase
ADP + myosin heavy chain kinase phosphate
show the reaction diagram
-
intermolecular autophosphorylation with vesicle-bound enzyme in absence of substrates
-
?
ATP + myosin heavy chain kinase
ADP + myosin heavy chain kinase phosphate
show the reaction diagram
-
intramolecular autophosphorylation
-
?
ATP + myosin heavy chain kinase
ADP + myosin heavy chain kinase phosphate
show the reaction diagram
-
intramolecular autophosphorylation
-
?
ATP + myosin heavy chain kinase
ADP + myosin heavy chain kinase phosphate
show the reaction diagram
-
intramolecular autophosphorylation
-
?
ATP + myosin heavy chain kinase
ADP + myosin heavy chain kinase phosphate
show the reaction diagram
-
intramolecular autophosphorylation
-
?
ATP + myosin heavy chain kinase
ADP + myosin heavy chain kinase phosphate
show the reaction diagram
-
intramolecular autophosphorylation
-
?
ATP + myosin heavy chain kinase
ADP + myosin heavy chain kinase phosphate
show the reaction diagram
-
intramolecular autophosphorylation
-
?
ATP + myosin heavy chain kinase
ADP + myosin heavy chain kinase phosphate
show the reaction diagram
P42527
intramolecular autophosphorylation
-
?
ATP + myosin heavy chain kinase
ADP + myosin heavy chain kinase phosphate
show the reaction diagram
P34125
intramolecular autophosphorylation
-
?
ATP + myosin heavy chain kinase
ADP + myosin heavy chain kinase phosphate
show the reaction diagram
Q869N2
enzyme incorporates 1 mol of phosphate per mol of enzyme
-
-
?
ATP + myosin heavy chain kinase
ADP + myosin heavy chain kinase phosphate
show the reaction diagram
-
4 phosphorylation sites on each heavy chain
-
?
ATP + myosin heavy chain kinase
ADP + myosin heavy chain kinase phosphate
show the reaction diagram
P34125
enzyme incorporates 20 mol phosphate per mol of kinase
-
?
ATP + myosin heavy chain kinase
ADP + myosin heavy chain kinase phosphate
show the reaction diagram
-
enzyme incorporates 2-3 mol phosphate per mol of 130 kDa subunit
-
?
ATP + myosin heavy chain kinase
ADP + myosin heavy chain kinase phosphate
show the reaction diagram
-
leads to activation of the phosphorylation activity towards myosin I
-
?
ATP + myosin heavy chain kinase
ADP + myosin heavy chain kinase phosphate
show the reaction diagram
-
leads to activation of the phosphorylation activity towards myosin I
-
?
ATP + myosin heavy chain kinase
ADP + myosin heavy chain kinase phosphate
show the reaction diagram
-
leads to activation of the phosphorylation activity towards myosin I
-
?
ATP + myosin heavy chain kinase
ADP + myosin heavy chain kinase phosphate
show the reaction diagram
-
leads to activation of the phosphorylation activity towards myosin I
-
?
ATP + myosin heavy chain kinase
ADP + myosin heavy chain kinase phosphate
show the reaction diagram
-
leads to activation of the phosphorylation activity towards myosin I
-
?
ATP + myosin heavy chain kinase
ADP + myosin heavy chain kinase phosphate
show the reaction diagram
-
leads to activation of the phosphorylation activity towards myosin I
-
?
ATP + myosin heavy chain kinase
ADP + myosin heavy chain kinase phosphate
show the reaction diagram
-
enzyme incorporates 6-8 mol phosphate per mol of enzyme
-
?
ATP + myosin heavy chain kinase
ADP + myosin heavy chain kinase phosphate
show the reaction diagram
P34125
the enzyme contains a cluster of 23 serine and threonine residues at the carboxyterminal end that might be the autophosphorylation domain, increased activity during chemotaxis
-
?
ATP + myosin heavy chain kinase
ADP + myosin heavy chain kinase phosphate
show the reaction diagram
Dictyostelium discoideum AX3
P34125
intramolecular autophosphorylation, enzyme incorporates 20 mol phosphate per mol of kinase, the enzyme contains a cluster of 23 serine and threonine residues at the carboxyterminal end that might be the autophosphorylation domain, increased activity during chemotaxis
-
?
ATP + myosin heavy-chain
ADP + myosin heavy chain phosphate
show the reaction diagram
P42527
-
-
-
?
ATP + myosin heavy-chain
ADP + myosin heavy chain phosphate
show the reaction diagram
P42527
role of RasGEF Q in regulating myosin II function through MHCK A, overview, phosphorylation of myosin takes place at three threonine residues in the tail region by myosin II heavy chain kinases
-
-
?
ATP + myosin I heavy chain
ADP + myosin I heavy chain phosphate
show the reaction diagram
-
-
-
?
ATP + myosin I heavy chain
ADP + myosin I heavy chain phosphate
show the reaction diagram
-
-
-
?
ATP + myosin I heavy chain
ADP + myosin I heavy chain phosphate
show the reaction diagram
-
-
-
?
ATP + myosin I heavy chain
ADP + myosin I heavy chain phosphate
show the reaction diagram
-
-
-
?
ATP + myosin I heavy chain
ADP + myosin I heavy chain phosphate
show the reaction diagram
-
-
-
?
ATP + myosin I heavy chain
ADP + myosin I heavy chain phosphate
show the reaction diagram
-
-
-
?
ATP + myosin I heavy chain
ADP + myosin I heavy chain phosphate
show the reaction diagram
-
-
-
?
ATP + myosin I heavy chain
ADP + myosin I heavy chain phosphate
show the reaction diagram
-
-
-
?
ATP + myosin I heavy chain
ADP + myosin I heavy chain phosphate
show the reaction diagram
O41467
-
-
?
ATP + myosin I heavy chain
ADP + myosin I heavy chain phosphate
show the reaction diagram
Q869N2
-
-
?
ATP + myosin I heavy chain
ADP + myosin I heavy chain phosphate
show the reaction diagram
Q93107
-
-
?
ATP + myosin I heavy chain
ADP + myosin I heavy chain phosphate
show the reaction diagram
-
-
-
?
ATP + myosin I heavy chain
ADP + myosin I heavy chain phosphate
show the reaction diagram
-
substrate: myosin IB, phosphorylation site is Ser315
-
?
ATP + myosin I heavy chain
ADP + myosin I heavy chain phosphate
show the reaction diagram
-
substrate: myosin IB, phosphorylation site is Ser315
-
?
ATP + myosin I heavy chain
ADP + myosin I heavy chain phosphate
show the reaction diagram
-
higher activity with membrane-bound substrate myosin I
-
?
ATP + myosin I heavy chain
ADP + myosin I heavy chain phosphate
show the reaction diagram
-
myosin light chains are no substrates
-
?
ATP + myosin I heavy chain
ADP + myosin I heavy chain phosphate
show the reaction diagram
-
myosin light chains are no substrates
-
?
ATP + myosin I heavy chain
ADP + myosin I heavy chain phosphate
show the reaction diagram
-
myosin light chains are no substrates
-
?
ATP + myosin I heavy chain
ADP + myosin I heavy chain phosphate
show the reaction diagram
-
substrate myosin IA: phosphorylation of a single threonine
-
?
ATP + myosin I heavy chain
ADP + myosin I heavy chain phosphate
show the reaction diagram
-
4 mol phosphate per mol of myosin
-
?
ATP + myosin I heavy chain
ADP + myosin I heavy chain phosphate
show the reaction diagram
-
phosphorylates serine-residues
-
?
ATP + myosin I heavy chain
ADP + myosin I heavy chain phosphate
show the reaction diagram
-
phosphorylation of residues Thr1833 and Thr2029
-
?
ATP + myosin I heavy chain
ADP + myosin I heavy chain phosphate
show the reaction diagram
-
phosphorylation of residues Thr1833 and Thr2029
-
?
ATP + myosin I heavy chain
ADP + myosin I heavy chain phosphate
show the reaction diagram
-
substrate is heavy chain of myosin IC
-
?
ATP + myosin I heavy chain
ADP + myosin I heavy chain phosphate
show the reaction diagram
Q93107
substrate is heavy chain of myosin IC
-
?
ATP + myosin I heavy chain
ADP + myosin I heavy chain phosphate
show the reaction diagram
-
substrate is heavy chain of myosin IC
-
?
ATP + myosin I heavy chain
ADP + myosin I heavy chain phosphate
show the reaction diagram
-
incorporation of 0.9-1.0 mol phosphate per mol of heavy chain myosin
-
?
ATP + myosin I heavy chain
ADP + myosin I heavy chain phosphate
show the reaction diagram
-
phosphorylates threonine residues
-
?
ATP + myosin I heavy chain
ADP + myosin I heavy chain phosphate
show the reaction diagram
-
phosphorylates threonine residues
-
?
ATP + myosin I heavy chain
ADP + myosin I heavy chain phosphate
show the reaction diagram
-
phosphorylates threonine residues
-
?
ATP + myosin I heavy chain
ADP + myosin I heavy chain phosphate
show the reaction diagram
-
phosphorylates threonine residues
-
?
ATP + myosin I heavy chain
ADP + myosin I heavy chain phosphate
show the reaction diagram
-
phosphorylates threonine residues
-
?
ATP + myosin I heavy chain
ADP + myosin I heavy chain phosphate
show the reaction diagram
-
1.9 mol phosphate per mol myosin
-
?
ATP + myosin I heavy chain
ADP + myosin I heavy chain phosphate
show the reaction diagram
-
10 mol phosphate per mol of kinase subunit
-
?
ATP + myosin I heavy chain
ADP + myosin I heavy chain phosphate
show the reaction diagram
-
20 mol phosphate per mol of kinase subunit, kinetics
-
?
ATP + myosin I heavy chain
ADP + myosin I heavy chain phosphate
show the reaction diagram
-
myosin I from intestinal brush border
-
?
ATP + myosin I heavy chain
ADP + myosin I heavy chain phosphate
show the reaction diagram
Q869N2
major site of phosphorylation is Ser8
-
?
ATP + myosin I heavy chain
ADP + myosin I heavy chain phosphate
show the reaction diagram
-
35 kDa trypsin fragment of the C-terminus of the maximally activated, phosphorylated enzyme is fully catalytically active and contains 2 thirds of the autophosphorylation sites of the native enzyme
-
?
ATP + myosin I heavy chain
ADP + myosin I heavy chain phosphate
show the reaction diagram
-
bovine muscle myosin is no substrate
-
?
ATP + myosin I heavy chain
ADP + myosin I heavy chain phosphate
show the reaction diagram
-
contains two myosin heavy chain kinases: one for myosin I and one for myosin II
-
?
ATP + myosin I heavy chain
ADP + myosin I heavy chain phosphate
show the reaction diagram
-
substrate: myosin IC, phosphorylation site is Ser311
-
?
ATP + myosin I heavy chain
ADP + myosin I heavy chain phosphate
show the reaction diagram
-
no substrates are human platelet myosin, ovalbumin and smooth muscle myosin from turkey
-
?
ATP + myosin I heavy chain
ADP + myosin I heavy chain phosphate
show the reaction diagram
-
a basic amino acid is essential on amino-terminal side of phosphorylation site, two are preferable, and a Tyr-residue is essential two residues away on the COOH-terminal side
-
?
ATP + myosin I heavy chain
ADP + myosin I heavy chain phosphate
show the reaction diagram
-
6-8 mol phosphate per mol of enzyme
-
?
ATP + myosin I heavy chain
ADP + myosin I heavy chain phosphate
show the reaction diagram
-
substrates are heavy chains of myosin IA and IB
-
?
ATP + myosin I heavy chain
ADP + myosin I heavy chain phosphate
show the reaction diagram
-
substrates are heavy chains of myosin IA and IB
-
?
ATP + myosin I heavy chain
ADP + myosin I heavy chain phosphate
show the reaction diagram
-
substrates are heavy chains of myosin IA and IB
-
?
ATP + myosin I heavy chain
ADP + myosin I heavy chain phosphate
show the reaction diagram
O41467
substrate: myosin ID
-
?
ATP + myosin I heavy chain
ADP + myosin I heavy chain phosphate
show the reaction diagram
Q869N2
substrate: myosin ID
-
?
ATP + myosin I heavy chain
ADP + myosin I heavy chain phosphate
show the reaction diagram
-
reaction in regulatory contractile activity in Dictyostelium discoideum
-
?
ATP + myosin I heavy chain
ADP + myosin I heavy chain phosphate
show the reaction diagram
-
involved in regulation of myosin II filament assembly
-
?
ATP + myosin I heavy chain
ADP + myosin I heavy chain phosphate
show the reaction diagram
-
involved in regulation of myosin II filament assembly, increased activity during chemotaxis
-
?
ATP + myosin I heavy chain
ADP + myosin I heavy chain phosphate
show the reaction diagram
Dictyostelium discoideum Ax-3
-
-, phosphorylation of residues Thr1833 and Thr2029, phosphorylates threonine residues, 10 mol phosphate per mol of kinase subunit, 6-8 mol phosphate per mol of enzyme
-
?
ATP + myosin II heavy chain
ADP + myosin II heavy chain phosphate
show the reaction diagram
-
-
-
?
ATP + myosin II heavy chain
ADP + myosin II heavy chain phosphate
show the reaction diagram
-, Q8MY12
-
-
?
ATP + myosin II heavy chain
ADP + myosin II heavy chain phosphate
show the reaction diagram
-
-
-
?
ATP + myosin II heavy chain
ADP + myosin II heavy chain phosphate
show the reaction diagram
-
-
-
?
ATP + myosin II heavy chain
ADP + myosin II heavy chain phosphate
show the reaction diagram
O76739, P42527, P90648
-
-
-
-
ATP + myosin II heavy chain
ADP + myosin II heavy chain phosphate
show the reaction diagram
P42527
-
-
?
ATP + myosin II heavy chain
ADP + myosin II heavy chain phosphate
show the reaction diagram
-
myosin light chains are no substrates
-
?
ATP + myosin II heavy chain
ADP + myosin II heavy chain phosphate
show the reaction diagram
-
contains two myosin heavy chain kinases: one for myosin I and one for myosin II
-
?
ATP + myosin II heavy chain
ADP + myosin II heavy chain phosphate
show the reaction diagram
-
specific isozyme A for the heavy chain of myosin II
-
?
ATP + myosin II heavy chain
ADP + myosin II heavy chain phosphate
show the reaction diagram
-
specific isozyme A for the heavy chain of myosin II
-
?
ATP + myosin II heavy chain
ADP + myosin II heavy chain phosphate
show the reaction diagram
-
incorporation of 3 mol phosphate per mol of myosin II heavy chain, phosphorylation sites are mainly identical in vitro and in vivo
-
?
ATP + myosin II heavy chain
ADP + myosin II heavy chain phosphate
show the reaction diagram
P90648
isozyme MHCK B
-
?
ATP + myosin II heavy chain
ADP + myosin II heavy chain phosphate
show the reaction diagram
-
phosphorylates serine residues
-
?
ATP + myosin II heavy chain
ADP + myosin II heavy chain phosphate
show the reaction diagram
-
phosphorylates serine residues
-
?
ATP + myosin II heavy chain
ADP + myosin II heavy chain phosphate
show the reaction diagram
-
drives filament disassembly in vitro
-
?
ATP + myosin II heavy chain
ADP + myosin II heavy chain phosphate
show the reaction diagram
P90648
drives filament disassembly in vitro
-
?
ATP + myosin II heavy chain
ADP + myosin II heavy chain phosphate
show the reaction diagram
O76739, P42527, P90648
catalytic domain
-
?
ATP + myosin II heavy chain
ADP + myosin II heavy chain phosphate
show the reaction diagram
-
phosphorylates primarly threonine residues
-
?
ATP + myosin II heavy chain
ADP + myosin II heavy chain phosphate
show the reaction diagram
O76739, P42527, P90648
phosphorylates primarly threonine residues
-
?
ATP + myosin II heavy chain
ADP + myosin II heavy chain phosphate
show the reaction diagram
-, Q8MY12
involved in regulation of myosin II filament assembly
-
?
ATP + myosin II heavy chain
ADP + myosin II heavy chain phosphate
show the reaction diagram
P90648
involved in regulation of myosin II filament assembly
-
?
ATP + myosin II heavy chain
ADP + myosin II heavy chain phosphate
show the reaction diagram
-
key role in regulating myosin localization
-
?
ATP + myosin II heavy chain
ADP + myosin II heavy chain phosphate
show the reaction diagram
P42527
key role in regulating myosin localization, the enzymes anterior localization is dynamically regulated during chemotaxis, phagocytosis, and other polarized cell motility events via direct binding to F-actin
-
?
ATP + myosin II heavy chain
ADP + myosin II heavy chain phosphate
show the reaction diagram
Dictyostelium discoideum JH10
-
specific isozyme A for the heavy chain of myosin II, drives filament disassembly in vitro, phosphorylates primarly threonine residues, key role in regulating myosin localization
-
?
ATP + myosin II heavy chain
ADP + myosin II heavy chain phosphate
show the reaction diagram
Q8MY12
-
-
?
ATP + myosin regulatory light chain
ADP + myosin regulatory light chain phosphate
show the reaction diagram
O76739, P42527, P90648
catalytic domain
-
-
?
ATP + peptide LMM58 of heavy chain
?
show the reaction diagram
-
4 mol phosphate per mol, Thr-residues are phosphorylated
-
-
?
ATP + phosvitin
ADP + phosvitin phosphate
show the reaction diagram
-
-
-
-
?
ATP + phosvitin
ADP + phosvitin phosphate
show the reaction diagram
-
no activity
-
-
-
ATP + phosvitin
ADP + phosvitin phosphate
show the reaction diagram
-
low activity
-
-
?
ATP + RKKFGESEKTKTKEFL
?
show the reaction diagram
P90648
isozyme MHCK B, synthetic peptide MH1
-
-
?
ATP + RKKFGESEKTKTKEFL-amide
?
show the reaction diagram
O76739, P42527, P90648
low activity
-
-
?
ATP + RKKFGESEKTKTKEFL-amide
?
show the reaction diagram
O76739, P42527, P90648
catalytic domain
-
-
?
ATP + RKKFGESEKTKTKEFL-amide
?
show the reaction diagram
-
isozyme myosin II heavy chain kinase A, synthetic peptide MH-3
-
-
?
ATP + RKKFGESEKTKTKEFL-amide
?
show the reaction diagram
O76739, P42527, P90648
synthetic peptide MH-3
-
-
?
ATP + smooth muscle myosin light chain
ADP + smooth muscle myosin light chain phosphate
show the reaction diagram
-
-
-
-
?
ATP + synthetic peptides
?
show the reaction diagram
-
-
-
-
?
ATP + synthetic peptides
?
show the reaction diagram
-
variations in length, and number, location and kind of basic residues of the basic sequence of peptide GRGRSSVYS, overview
-
-
?
ATP + synthetic peptides
?
show the reaction diagram
-
peptide MH-3, corresponding to myosin II heavy chain from residues 2020 to 2035 except that Ser-2026 and Thr-2031 have been replaced by alanine
-
-
?
ATP + troponin T
ADP + troponin T phosphate
show the reaction diagram
-
-
-
-
?
ATP + YAYDTRYRR
?
show the reaction diagram
O76739, P42527, P90648
consensus sequence
-
-
?
ATP + YAYDTRYRR
?
show the reaction diagram
O76739, P42527, P90648
catalytic domain of the enzyme
-
-
?
ATP + [myosin heavy-chain]
ADP + [myosin heavy-chain] phosphate
show the reaction diagram
-
-
-
-
?
ATP + [myosin heavy-chain]
ADP + [myosin heavy-chain] phosphate
show the reaction diagram
P90648
-
-
-
?
ATP + [myosin heavy-chain]
ADP + [myosin heavy-chain] phosphate
show the reaction diagram
-
phosphorylation of sites within the MHC alpha-helical, coiled-coil tail by MHCK A
-
-
?
ATP + [myosin-heavy-chain]
ADP + [myosin-heavy-chain]phosphate
show the reaction diagram
P42527
-
-
-
?
additional information
?
-
-
substrate specificity study
-
-
-
additional information
?
-
Q93107
enzyme contains several SH3-binding domains
-
-
-
additional information
?
-
-
the Mg2+-ATPase activity of the substrate myosin I is increased by its phosphorylation and the binding of F-actin
-
-
-
additional information
?
-
O41467
enzyme possesses binding domains for the Ras-related GTP-binding proteins Cdc42 and Rac
-
-
-
additional information
?
-
Q93107
enzyme possesses binding domains for the Ras-related GTP-binding proteins Cdc42 and Rac
-
-
-
additional information
?
-
-
the Mg2+-ATPase activity of the substrate myosin II is inhibited in vitro by its phosphorylation
-
-
-
additional information
?
-
P90648
the Mg2+-ATPase activity of the substrate myosin II is inhibited in vitro by its phosphorylation
-
-
-
additional information
?
-
-
localization of autophosphorylation sites
-
-
-
additional information
?
-
O76739, P42527, P90648
localization of autophosphorylation sites
-
-
-
additional information
?
-
P42527
biochemical mechanism for the spatial regulation of myosin II filament disassembly acts via MHCK A activation by actin
-
-
-
additional information
?
-
P42527
C-terminal phosphorylation of myosin heavy chain is required for regulation of myosin II filament assembly, regulation mechanism
-
-
-
additional information
?
-
-
C-terminal phosphorylation of myosin heavy chain is required for regulation of myosin II filament assembly, the 3 isozymes MHCK A, MHCK B, and MHCK C show differential localization patterns in living cells
-
-
-
additional information
?
-
P42527
MHCK A performs autophosphorylation
-
-
-
additional information
?
-
P42527
MHCK A contains active RasB, and is the predominant exchange factor for RasB. RasGEF Q can bind to F-actin and has the potential to form complexes with MHCK A, overview
-
-
-
additional information
?
-
P42527
substrate specificity of the MHCK A catalytic domain: a lysine or arginine in the P+1 position on the C-terminal side of the phosphoacceptor threonine, P site, is critical for peptide substrate recognition by MHCK A. Phosphorylation by MHCK A is enhanced 2 to 4fold by basic residues in the P+2, P+3 and P+4 positions, with a strong preference for threonine as the phosphoacceptor amino acid, overview, substrate specificity of the MHCK B catalytic domain: a lysine or arginine in the P+1 position on the C-terminal side of the phosphoacceptor threonine, P site, is critical for peptide substrate recognition by MHCK B. Phosphorylation by MHCK B is further enhanced 8fold by a basic residue in the P+2 position, strong preference for threonine as the phosphoacceptor amino acid, overview
-
-
-
additional information
?
-
-
the enzyme also exhibits ATPase and unspecific Ser/Thr protein kinase activities
-
-
-
additional information
?
-
-
the enzyme performs autophosphorylation at Thr825
-
-
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
ATP + myosin heavy chain
ADP + myosin heavy chain phosphate
show the reaction diagram
-
-
-
?
ATP + myosin heavy chain
ADP + myosin heavy chain phosphate
show the reaction diagram
-
-
-
?
ATP + myosin heavy chain
ADP + myosin heavy chain phosphate
show the reaction diagram
-
-
-
?
ATP + myosin heavy chain kinase
ADP + myosin heavy chain kinase phosphate
show the reaction diagram
P34125
intramolecular autophosphorylation, increased activity during chemotaxis
-
?
ATP + myosin heavy chain kinase
ADP + myosin heavy chain kinase phosphate
show the reaction diagram
Dictyostelium discoideum AX3
P34125
intramolecular autophosphorylation, increased activity during chemotaxis
-
?
ATP + myosin heavy-chain
ADP + myosin heavy chain phosphate
show the reaction diagram
P42527
-
-
-
?
ATP + myosin heavy-chain
ADP + myosin heavy chain phosphate
show the reaction diagram
P42527
role of RasGEF Q in regulating myosin II function through MHCK A, overview
-
-
?
ATP + myosin I heavy chain
ADP + myosin I heavy chain phosphate
show the reaction diagram
-
-
-
?
ATP + myosin I heavy chain
ADP + myosin I heavy chain phosphate
show the reaction diagram
-
-
-
?
ATP + myosin I heavy chain
ADP + myosin I heavy chain phosphate
show the reaction diagram
-
-
-
?
ATP + myosin I heavy chain
ADP + myosin I heavy chain phosphate
show the reaction diagram
-
-
-
?
ATP + myosin I heavy chain
ADP + myosin I heavy chain phosphate
show the reaction diagram
-
-
-
?
ATP + myosin I heavy chain
ADP + myosin I heavy chain phosphate
show the reaction diagram
-
-
-
?
ATP + myosin I heavy chain
ADP + myosin I heavy chain phosphate
show the reaction diagram
-
-
-
?
ATP + myosin I heavy chain
ADP + myosin I heavy chain phosphate
show the reaction diagram
-
-
-
?
ATP + myosin I heavy chain
ADP + myosin I heavy chain phosphate
show the reaction diagram
O41467
-
-
?
ATP + myosin I heavy chain
ADP + myosin I heavy chain phosphate
show the reaction diagram
Q869N2
-
-
?
ATP + myosin I heavy chain
ADP + myosin I heavy chain phosphate
show the reaction diagram
Q93107
-
-
?
ATP + myosin I heavy chain
ADP + myosin I heavy chain phosphate
show the reaction diagram
-
-
-
?
ATP + myosin I heavy chain
ADP + myosin I heavy chain phosphate
show the reaction diagram
-
reaction in regulatory contractile activity in Dictyostelium discoideum
-
?
ATP + myosin I heavy chain
ADP + myosin I heavy chain phosphate
show the reaction diagram
-
involved in regulation of myosin II filament assembly
-
?
ATP + myosin I heavy chain
ADP + myosin I heavy chain phosphate
show the reaction diagram
-
involved in regulation of myosin II filament assembly, increased activity during chemotaxis
-
?
ATP + myosin I heavy chain
ADP + myosin I heavy chain phosphate
show the reaction diagram
Dictyostelium discoideum Ax-3
-
-
-
?
ATP + myosin II heavy chain
ADP + myosin II heavy chain phosphate
show the reaction diagram
-
-
-
?
ATP + myosin II heavy chain
ADP + myosin II heavy chain phosphate
show the reaction diagram
-
-
-
?
ATP + myosin II heavy chain
ADP + myosin II heavy chain phosphate
show the reaction diagram
-
-
-
?
ATP + myosin II heavy chain
ADP + myosin II heavy chain phosphate
show the reaction diagram
O76739, P42527, P90648
-
-
-
-
ATP + myosin II heavy chain
ADP + myosin II heavy chain phosphate
show the reaction diagram
-, Q8MY12
-
-
?
ATP + myosin II heavy chain
ADP + myosin II heavy chain phosphate
show the reaction diagram
-, Q8MY12
involved in regulation of myosin II filament assembly
-
?
ATP + myosin II heavy chain
ADP + myosin II heavy chain phosphate
show the reaction diagram
P90648
involved in regulation of myosin II filament assembly
-
?
ATP + myosin II heavy chain
ADP + myosin II heavy chain phosphate
show the reaction diagram
-
key role in regulating myosin localization
-
?
ATP + myosin II heavy chain
ADP + myosin II heavy chain phosphate
show the reaction diagram
P42527
key role in regulating myosin localization, the enzymes anterior localization is dynamically regulated during chemotaxis, phagocytosis, and other polarized cell motility events via direct binding to F-actin
-
?
ATP + myosin II heavy chain
ADP + myosin II heavy chain phosphate
show the reaction diagram
Dictyostelium discoideum JH10
-
key role in regulating myosin localization
-
?
ATP + myosin II heavy chain
ADP + myosin II heavy chain phosphate
show the reaction diagram
Q8MY12
-
-
?
ATP + [myosin heavy-chain]
ADP + [myosin heavy-chain] phosphate
show the reaction diagram
-
-
-
-
?
ATP + [myosin heavy-chain]
ADP + [myosin heavy-chain] phosphate
show the reaction diagram
P90648
-
-
-
?
ATP + [myosin-heavy-chain]
ADP + [myosin-heavy-chain]phosphate
show the reaction diagram
P42527
-
-
-
?
additional information
?
-
P42527
biochemical mechanism for the spatial regulation of myosin II filament disassembly acts via MHCK A activation by actin
-
-
-
additional information
?
-
P42527
C-terminal phosphorylation of myosin heavy chain is required for regulation of myosin II filament assembly, regulation mechanism
-
-
-
additional information
?
-
-
C-terminal phosphorylation of myosin heavy chain is required for regulation of myosin II filament assembly, the 3 isozymes MHCK A, MHCK B, and MHCK C show differential localization patterns in living cells
-
-
-
additional information
?
-
P42527
MHCK A contains active RasB, and is the predominant exchange factor for RasB. RasGEF Q can bind to F-actin and has the potential to form complexes with MHCK A, overview
-
-
-
METALS and IONS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
Ca2+
-
requirement, Ca2+/calmodulin-dependent isozyme
Ca2+
-
not required
Ca2+
-
slightly activates unphosphorlyated enzyme
KCl
P42527
activates
Mg2+
-
absolutely requires 1-2 mM Mg2+; cannot be substituted by Ca2+ or Mn2+; requirement
Mg2+
-
requirement
Mg2+
-
maximal activity at 6-8 mM; requirement
Mg2+
-
absolutely requires 1-2 mM Mg2+; requirement
Mg2+
-
cannot be substituted by Ca2+ or Mn2+; requirement
Mg2+
-
optimal activation at 6 mM; requirement
Mg2+
-
requirement
Mg2+
P90648
required
Mg2+
-
required, the Mg2 binding sites are regulatory, because millimolar concentrations of Mg2+, in excess of that required to bind to ATP, are required for A-CAT to exhibit maximal catalytic activity
Mg2+
-
required, Mg2+ is coordinated in an octahedral arrangement by the side chains of Asp766 and Gln768, the main-chain carbonyl group of Pro767, and three water molecules
additional information
-
no activation by Mn2+
additional information
-
no activation by Mn2+
INHIBITORS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
Ca2+/calmodulin
-
no inhibition
-
Ca2+/calmodulin
-
no inhibition
-
Ca2+/calmodulin
-
weak
-
Ca2+/calmodulin
-
no inhibition
-
Ca2+/calmodulin
Q869N2
binds to the enzyme and inhibits its activation by acidic phospholipids but not by guanosine 5'-3-O-(thio)triphosphate-Rac1
-
Ca2+/calmodulin
-
calmodulin-binding site: amino acid residues 51-80; competes with phospholipids
-
heparin
-
-
KCl
-
strong, 90% inhibition at 60 mM, complete inhibition at 100 mM
KCl
-
80% inhibition at 90 mM
Myosin I
-
inhibits autophosphorylation
-
NaCl
-
above 0.1 M
Positively charged polypeptides
-
strong inhibition, e.g. poly-(D-Lys), poly-(L-Lys), poly-(L-Arg) of different molecular weights
-
KCl
-
60% inhibition at 0.1 M
additional information
-
no inhibition by Ca2+; no inhibition by cAMP or cGMP
-
additional information
-
ionic strength has no effect on autophosphorylation activity; strong inhibition of phosphorylation activity by increasing ionic strength
-
additional information
-
strong inhibition of phosphorylation activity by increasing ionic strength
-
additional information
-
no inhibition by cAMP or cGMP
-
additional information
-
autoinhibitory domains, overview, autoinhibition is reversed by Rac
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
acidic phospholipids
-
enhance the activation of the enzyme by autophosphorylation
-
acidic phospholipids
Q869N2
enhance the activation of the enzyme by autophosphorylation; functions cooperatively with acidic phospholipids to associate the enzyme with membranes
-
DNA
-
autophosphorylation activity is increased 5-10fold in a Ca2+-independent manner
F-actin
P42527
i.e. filamentous actin, from rabbit muscle, about 40fold activation, coiled-coil domain binding structure and mechanism, overview, the enzyme's coiled-coil structure mediates its oligomerization, cellular localization, and actin-binding activity of the MHCK A
-
F-actin
P42527
about 40fold activation of myosin heavy chain kinase A, structure and mechanism, stimulation via enzyme autophosphorylation
-
G-actin
P42527
slight activation of MHCK A, activation is abolished by latrunculin A, which depolymerizes the actin filament
-
guanosine 5'-3-O-(thio)triphosphate-Rac1
Q869N2
10fold activation of autophosphorylation and kinase activity; functions cooperatively with acidic phospholipids to associate the enzyme with membranes; i.e. GTPgammaS-Rac1
-
phosphatidylinositol
Q869N2
10fold activation of autophosphorylation and kinase activity
phosphatidylinositol
-
-
phosphatidylinositol 4,5-bisphosphate
Q869N2
10fold activation of autophosphorylation and kinase activity
phosphatidylserine
-
stimulates the enzymes autophosphorylation activity
phosphatidylserine
-
stimulation only of the autophosphorylated enzyme
phosphatidylserine
Q869N2
10fold activation of autophosphorylation and kinase activity
Phospholipid vesicles
-
autophosphorylation activity is increased 5-10fold in a Ca2+-independent manner; composed of phosphatidylserine or phosphatidylinositol, not phosphatidylcholine
-
Phospholipid vesicles
-
autophosphorylation activity is increased 5-10fold in a Ca2+-independent manner; composed of phosphatidylethanolamine; composed of phosphatidylserine or phosphatidylinositol, not phosphatidylcholine
-
Rac
-
activation of autophosphorylation and kinase activity only in presence of phosphatidylserine, activates only the fully phosphorylated enzyme; linoleic acid supports activation by Rac
-
Rac
-
reverses autoinhibition of the enzyme
-
heparin
-
autophosphorylation activity is increased 5-10fold in a Ca2+-independent manner
additional information
-
no activation by calmodulin, cAMP; no activation by cGMP; no activation by EGTA
-
additional information
-
-
-
additional information
-
no activation by calmodulin, cAMP; no activation by cGMP
-
additional information
-
enzyme is stimulated by its autophosphorylation
-
additional information
-
no activation by calmodulin, cAMP
-
additional information
-
no activation by calmodulin, cAMP; no activation by cGMP
-
additional information
-
enzyme is stimulated by its autophosphorylation
-
additional information
-
-
-
additional information
Q869N2
enzyme is stimulated by its autophosphorylation; no activation by phosphatidylcholine and sphingosine
-
additional information
-
no activation by phosphatidylcholine and phosphatidylethanolamine
-
additional information
-
association with the actin cytoskeleton causes a drastic increase in the autophosphorylation activity of MHCK A, which is then activated
-
additional information
-
autophosphorylation at Thr825 activates MHCK A at least 50fold, dephosphorylation of the residue reduces the activity
-
KM VALUE [mM]
KM VALUE [mM] Maximum
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.098
-
AKRVSMMR
Q869N2
in presence of guanosine 5'-3-O-(thio)triphosphate-Rac1, pH 7.0
0.116
-
AKRVSMMR
Q869N2
in presence of phosphatidylserine, pH 7.0
0.043
-
ATP
-
pH 7.5, 30C
0.16
-
ATP
-
recombinant wild-type catalytic domain, pH 7.0, 30C
0.3
-
ATP
-
recombinant T632A mutant catalytic domain, pH 7.0, 30C
0.05
-
GRGRSSVYS
-
pH 7.5, 30C
-
0.05
-
GRGRSSVYS
-
pH 7.0, 30C
-
0.064
-
GRGRSSVYS
-
phospholipid-bound, unphosphorylated enzyme, pH 7.0, 30C; soluble, phosphorylated enzyme, pH 7.0, 30C
-
0.11
-
GRGRSSVYS
-
soluble, unphosphorylated enzyme, pH 7.0, 30C
-
0.15
-
GRGRSSVYS
-
recombinant wild-type catalytic domain, pH 7.0, 30C
-
0.2
-
GRGRSSVYS
-
recombinant T632A mutant catalytic domain, pH 7.0, 30C
-
0.016
-
GRSARVSTYA
Q869N2
pH 7.0
-
0.017
-
GRSARVSTYA
Q869N2
in presence of guanosine 5'-3-O-(thio)triphosphate-Rac1, pH 7.0
-
0.015
-
myosin heavy chain
-
pH 7.5, 22C
-
0.0003
-
myosin IA
-
soluble, unphosphorylated enzyme, pH 7.0, 30C
-
0.0007
-
myosin IA
-
phospholipid-bound, unphosphorylated enzyme, pH 7.0, 30C
-
0.0023
-
myosin IA
-
soluble, phosphorylated enzyme, pH 7.0, 30C
-
0.0002
-
myosin IB
-
soluble, unphosphorylated enzyme, pH 7.0, 30C
-
0.0005
-
myosin IB
-
phospholipid-bound, unphosphorylated enzyme, pH 7.0, 30C
-
0.0055
-
myosin IB
-
soluble, phosphorylated enzyme, pH 7.0, 30C
-
0.015
-
protein LMM58 heavy chain
-
pH 7.5, 22C
-
0.22
-
RKKFGESEKTKTKEFL
-
recombinant MHCK B, pH 7.0, 22C
-
0.1
-
RKKFGESEKTKTKEFL-amide
-
pH 7.5, 25C
-
0.28
-
RKKFGESEKTKTKEFL-amide
O76739, P42527, P90648
pH 7.0, 25C
-
0.55
-
YAYDTRYRR
O76739, P42527, P90648
pH 7.0, 25C
-
0.019
-
GRSARVSTYA
Q869N2
in presence of phosphatidylserine, pH 7.0
-
additional information
-
additional information
-
Km values for derivatives of peptide GRGRSSVYS
-
additional information
-
additional information
-
catalytic domain mutants
-
additional information
-
additional information
P42527
F-actin binding kinetics
-
additional information
-
additional information
P42527
kinetics; kinetics
-
TURNOVER NUMBER [1/s]
TURNOVER NUMBER MAXIMUM[1/s]
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
5
-
AKRVSMMR
Q869N2
in presence of guanosine 5'-3-O-(thio)triphosphate-Rac1, pH 7.0
5.4
-
AKRVSMMR
Q869N2
in presence of phosphatidylserine, pH 7.0
71
-
GRGRSSVYS
-
recombinant wild-type catalytic domain, pH 7.0, 30C
-
105
-
GRGRSSVYS
-
recombinant T632A mutant catalytic domain, pH 7.0, 30C
-
0.3
-
GRSARVSTYA
Q869N2
pH 7.0
-
4.6
-
GRSARVSTYA
Q869N2
in presence of guanosine 5'-3-O-(thio)triphosphate-Rac1, pH 7.0
-
0.01
-
RKKFGESEKTKTKEFL-amide
O76739, P42527, P90648
pH 7.0, 25C
-
0.55
-
RKKFGESEKTKTKEFL-amide
O76739, P42527, P90648
pH 7.0, 25C
-
0.79
-
RKKFGESEKTKTKEFL-amide
O76739, P42527, P90648
pH 7.0, 25C
-
14
-
YAYDTRYRR
O76739, P42527, P90648
pH 7.0, 25C
-
4.7
-
GRSARVSTYA
Q869N2
in presence of phosphatidylserine, pH 7.0
-
additional information
-
additional information
-
catalytic domain mutants
-
additional information
-
additional information
O76739, P42527, P90648
catalytic domain, several substrates
-
Ki VALUE [mM]
Ki VALUE [mM] Maximum
INHIBITOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
additional information
-
additional information
-
inhibition by positively charged polypeptides
-
SPECIFIC ACTIVITY [µmol/min/mg]
SPECIFIC ACTIVITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
0.00032
-
-
partially purified enzyme
0.00063
-
-
purified enzyme
0.98
-
-
purified enzyme
0.98
-
-
purified enzyme; substrate myosin II heavy chain
2.1
-
-
purified enzyme
3.03
-
-
purified enzyme, substrate histone 2A, 0.067 mM
4.6
-
-
purified enzyme, substrate myosin IB, 0.0024 mM
additional information
-
-
-
pH OPTIMUM
pH MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
7
7.5
-
-
7
-
Q869N2
assay at
7
-
O76739, P42527, P90648
assay at; assay at; assay at
7
-
P42527
assay at; assay at
7.5
-
-
assay at
8
-
P42527
actin binding assay at
8
-
P42527
assay at
pH RANGE
pH RANGE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
6
8.5
-
about 50% activity at pH 6.0; about half-maximal activity at pH 6.0
6
8.5
-
about 80% activity at pH 6.0; about half-maximal activity at pH 6.0
6
9
-
about half-maximal activity at pH 6.0, about 90% of maximal activity at pH 7.0 and pH 9.0
TEMPERATURE OPTIMUM
TEMPERATURE OPTIMUM MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
20
-
P42527
actin binding assay at
25
-
O76739, P42527, P90648
assay at; assay at; assay at
25
-
P42527
assay at
25
-
P42527
assay at; assay at
30
-
-
assay at
SOURCE TISSUE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
SOURCE
-
growth-phase cells contain enzyme form MHCK A; starved-developing cells contain enzyme form MHCK B
Manually annotated by BRENDA team
-
starved, developing cells
Manually annotated by BRENDA team
Dictyostelium discoideum Ax-3, Dictyostelium discoideum JH10
-
-
-
Manually annotated by BRENDA team
-
overexpresssing cells show slower growth and increased cell size
Manually annotated by BRENDA team
Dictyostelium discoideum JH10
-
overexpresssing cells show slower growth and increased cell size
-
Manually annotated by BRENDA team
-
of the intestine, brush border cells
Manually annotated by BRENDA team
additional information
P34125
enzyme expression only during development
Manually annotated by BRENDA team
additional information
Dictyostelium discoideum AX3
-
enzyme expression only during development
-
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
MHCK A associates with the cytoskeleton and localizes to the cell cortex
Manually annotated by BRENDA team
-
binding to the plasma membrane enhances the activity of unphosphorylated enzyme 20fold, substrate myosin I
Manually annotated by BRENDA team
Q869N2
association of the enzyme to membranes enhances the activity
Manually annotated by BRENDA team
Dictyostelium discoideum AX3
-
bound
-
Manually annotated by BRENDA team
additional information
-, Q8MY12
MHCK A is localized to actin-rich regions in mitotic cells
-
Manually annotated by BRENDA team
additional information
P42527
translocation of the enzyme within the cell responding to outer signals
-
Manually annotated by BRENDA team
additional information
P42527
the enzyme's coiled-coil structure mediates its oligomerization, cellular localization, and actin-binding activity of the MHCK A
-
Manually annotated by BRENDA team
additional information
-
the 3 isozymes MHCK A, MHCK B, and MHCK C show differential localization patterns in living cells, overview
-
Manually annotated by BRENDA team
MOLECULAR WEIGHT
MOLECULAR WEIGHT MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
107000
-
-
gel filtration
130000
-
-
MHCK A
160000
-
-
gel filtration
240000
-
-
gel filtration
490000
-
-
gel filtration, sucrose density gradient centrifugation
700000
-
-
above, gel filtration
SUBUNITS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
?
-
x * 84000, SDS-PAGE; x * 94000, phosphorylated enzyme, SDS-PAGE
?
-
x * 130000, SDS-PAGE
?
-, Q8MY12
; x * 86000, DNA sequence determination
?
-
x * 79300, determined from amino acid sequence, difference to MW of 97 kDa determined by SDS-PAGE is due to high proline content
?
-
x * 145000, phosphorylated MHCK A, SDS-PAGE, x * 130000, unphosphorylated MHCK A, SDS-PAGE
?
-
x * 86000, DNA sequence determination
-
?
Dictyostelium discoideum Ax-3
-
x * 130000, SDS-PAGE
-
decamer
-
10 * 50000, SDS-PAGE, asymmetric complex with an axial ratio calculated for prolate ellipsoid of 6.1
monomer
-
1 * 107000, phosphorylated enzyme, SDS-PAGE; 1 * 97000, unphosphorylated enzyme, SDS-PAGE
monomer
-
1 * 107000, phosphorylated enzyme, SDS-PAGE
additional information
P42527
the enzyme's coiled-coil structure mediates its oligomerization, cellular localization, and actin-binding activity of the MHCK A
additional information
-
MHCK domain organization
additional information
-
MHCK A protein consists of an N-terminal coiled-coil domain, a central kinase domain, and a C-terminal WD-repeat domain, domain structures comparisons of the catalytic alpha-kinase domain to the one from Mus musculus, overview
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
phosphoprotein
P42527
MHCK A performs autophosphorylation, facilitated by F-actin requiring the coiled coil domain of the enzyme
phosphoprotein
-
association with the actin cytoskeleton causes a drastic increase in the autophosphorylation activity of MHCK A, which is then activated
phosphoprotein
P90648
15 to 20 autophosphorylation sites in MHCK-B reside in the N-rich region of the kinase. Autophosphorylation of full-length MHCK-B has no effect on the kinase activity of the enzyme
phosphoprotein
-
autophosphorylation at Thr825 activates MHCK A at least 50fold, dephosphorylation of the residue reduces the activity. The phosphorylated Thr825 docks intramolecularly into the phosphate-pocket. Allosteric activation is predicted to involve a conformational change in Arg734, which bridges the bound phosphate to Asp762 in a key active site loop
Crystallization/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
MHCK A in complex with ATP and a peptide substrate, and MHCK A alpha kinase domain in individual complexes with AMP, ADP, and beta,gamma-methyleneadenosine 5'-triphosphate, X-ray diffraction structcure determination and analysis
-
purified recombinant wild-type and truncation mutant enzymes, hanging drop vapor diffusion method, mixing of 0.001 ml protein solution with 0.001 ml of reservoir solution containing 0.1 M Tris-HCl, pH 8.5, 0.2 M NaH2PO4, and 18% w/v PEG 8000, 4C, 10 days, X-ray diffraction structure determination and analysis at 1.9 A resolution
-
pH STABILITY
pH STABILITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
8
-
-
and above, unstable
TEMPERATURE STABILITY
TEMPERATURE STABILITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
25
-
-
1-2 h, stable
GENERAL STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
loses about 25% of activity for every freeze-thaw cycle
-
phosphorylated enzyme is somewhat less stable than unphosphorylated enzyme
-
very unstable if exposed to low salt, i.e. 50 mM KCl or less, in the absence of sucrose
-
freeze-thawing inactivates
-
STORAGE STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
-20C, in 50% glycerol, 3 months stable and less than 20% loss of activity within 6 months
-
-20C, purified, stable up to 1 year
-
4C, several months
-
-20C, in 25 mM HEPES buffer, pH 7.5, 1 mM DTT, 1 mM EDTA, 50 mM NaCl, 10% glycerol, or 20% sucrose, stable for 3 months
-
-20C, in 50% sucrose or glycerol, t1/2: 2 weeks
-
0C, highly purified preparation of unphosphorylated enzyme, 25% loss of activity per day
-
0C, in 10 mM imidazole, pH 7, 100 mM KCl, 2 mM DTT, 60% sucrose, several weeks
-
0C, partially purified preparation of unphosphorylated enzyme, several days
-
indefinitely stable upon storage in liquid nitrogen, recovery of 60-70% activity after thawing
-
0C, at least 1 month
-
0C, further purified Ca2+/calmodulin-dependent isozyme, complete loss of activity within 1 day
-
0C, partly purified Ca2+/calmodulin-dependent isozyme, at least 2 weeks
-
Purification/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
affinity chromatography using histone-resin
-
affinity chromatography using histone-resin; to near homogeneity
-
recombinant His-tagged catalytic domains, wild-type and mutants, from Sf9 insect cells
-
recombinant peptides of the enzymes N-terminus from Escherichia coli, His- or FLAG-tagged, and recombinant enzyme from Sf9 insect cells
-
enzyme copurifies with casein kinase II and Ca2+-independent myosin kinase
-
14000fold to near homogeneity
-
isolation of highly phosphorylated and unphosphorylated myosin II heavy chain kinase A
-
MHCK B, recombinant from Dictyostelium discoideum cells as FLAG-tagged protein
-
recombinant GST-fusion catalytic domain of MHCK B, expressed in Escherichia coli; recombinant His-tagged catalytic domain of MHCK A, expressed in Escherichia coli; recombinant His-tagged catalytic domain of MHCK C, expressed in Escherichia coli
O76739, P42527, P90648
recombinant GST-tagged wild-type full-length and MHCKB truncation mutants by glutathione affinity chromatography
P90648
recombinant His-tagged full-length isozyme MHCK A and truncation mutant DELTAcoil-MHCK A from Dictyostelium discoideum to homogeneity by affinity chromatography, recombinant GST-fusion coiled-coil domain and catalytic domain from Escherichia coli to near homogeneity by affinity chromatography
P42527
recombinant His-tagged full-length isozyme MHCK A from Dictyostelium discoideum by affinity chromatography, recombinant GST-fusion truncation mutant DELTAcoil-MHCK A from Escherichia coli by affinity chromatography, the GST-tag is cleaved off by thrombin treatment
P42527
recombinant His-tagged or GFP-fusion proteins from Dictyostelium discoideum
P42527
recombinant His-tagged wild-type and mutant MHCK A alpha-kinase domains from Escherichia coli strain BL21(DE3) by nickel affinity chromatography
-
recombinant MHCK A GST-tagged catalytic domain by glutathione affinity chromatography; recombinant MHCK B GST-tagged catalytic domain by glutathione affinity chromatography
P42527
solubilized by high-salt extraction, affinity chromatography, 4600fold, to homogeneity
-
Ca2+/calmodulin-dependent heavy chain kinase, 84fold
-
separation of the Ca2+/calmodulin-dependent and -independent isozymes
-
Cloned/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
cloning of wild-type and mutants of the catalytic domain of myosin I heavy chain kinase as His-tagged proteins and expression in Spodoptera frugiperda Sf9 cells via baculovirus infection system
-
construction of His-tagged or FLAG-tagged N-terminal enzyme peptides by site directed mutagenesis for introduction of start and stop codons, expression in Escherichia coli BL21(DE3); subcloning and expression in Escherichia coli, expression in Spodoptera frugiperda Sf9 cells via baculovirus infection system
-
DNA and amino acid sequence determination and analysis
-
cells overexpressing GFP-GEF have both unphosphorylated and autophosphorylated MHCK A
-
construction of His-tagged or GFP fusion proteins with the full length enzyme or enzyme fragments, expression in Dictyostelium discoideum cells
P42527
DNA sequence determination and analysis
-
DNA sequence determination and analysis, gene MHCK possesses all of the domains characteristic of members of the protein kinase C family
P34125
expression of FLAG-tagged T825A and T825E enzyme mutants in Dictyostelium discoideum cells, expression of His-tagged wild-type and mutant MHCK A alpha-kinase domains in Escherichia coli strain BL21(DE3)
-
expression of GFP-tagged isozyme MHCK A in a Dictyostelium discoideum strain lacking endogenous MHCK A, expression of a truncation mutant DELTAcoil-MHCK A comprising residues 1-498 in Escherichia coli as GST-fused protein
P42527
expression of MHCK A, comprising residues 527-887, i.e. A-CAT, as a GST-fusion protein, phylogenetic analysis; expression of MHCK B, comprising residues 13-459, i.e. B-CAT, as a GST-fusion protein, phylogenetic analysis
P42527
expression of the 3 isozymes MHCK A, MHCK B, and MHCK C as GFP-fusion proteins
-
expression of the catalytic domain of MHCK B as a GST-fusion protein in Escherichia coli BL21(DE3); expression of the His-tagged catalytic domain of MHCK A in Escherichia coli BL21(DE3); expression of the His-tagged catalytic domain of MHCK C in Escherichia coli BL21(DE3)
O76739, P42527, P90648
gene mhck A, construction of overexpressing cell line by transfection of an expression plasmid into the deficient mhck A- cell line
-
MHCK B, overexpression as FLAG-tagged protein in AX2 cells or 3xALA cells of Dictyostelium discoideum
-
overexpression of FLAG-tagged full-length MHCK-B in Dictyostelium cells, in AX2, mhkB-null, and mhkA/B/C-null cell lines. Expression of GST-tagged wild-type full-length and MHCKB truncation mutants
P90648
overexpression of His-tagged full-length isozyme MHCK A and truncation mutant DELTAcoil-MHCK A comprising residues 1-498 in Dictyostelium discoideum, overexpression of isolated coiled-coil domain and of the catalytic domain in Escherichia coli as GST-fused proteins
P42527
ENGINEERING
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
S627A
-
catalytic domain mutant, mutation of potential phosphorylation site, no phosphorylation of the mutant, reduced activity, increased Km values for the substrates, but higher activity than the unphosphorylated wild-type enzyme
S627D
-
catalytic domain mutant, mutation of potential phosphorylation site, no phosphorylation of the mutant, reduced activity, increased Km values for the substrates, the acidic residue cannot substitute for phospho-Ser
S627E
-
catalytic domain mutant, mutation of potential phosphorylation site, no phosphorylation of the mutant, reduced activity, increased Km values for the substrates, the acidic residue cannot substitute for phospho-Ser
T631A
-
catalytic domain mutant, mutation of a conserved Thr residue, full phosphorylation of the mutant, reduced activity, increased Km values for the substrates
T631D
-
catalytic domain mutant, mutation of a conserved Thr residue, 95% phosphorylation of the mutant, highly reduced activity, increased Km values for the substrates
T631E
-
catalytic domain mutant, mutation of a conserved Thr residue, no phosphorylation of the mutant, highly reduced activity, highly increased Km values for the substrates
T632A
-
catalytic domain mutant, mutation of a nonconserved Thr residue, full phosphorylation of the mutant, increased activity, only slightly increased Km values for the substrates
T632D
-
catalytic domain mutant, mutation of a nonconserved Thr residue, 80% phosphorylation of the mutant, reduced activity, increased Km values for the substrates
T632E
-
catalytic domain mutant, mutation of a nonconserved Thr residue, full phosphorylation of the mutant, reduced activity, increased Km values for the substrates
C800A
P42527
catalytic domain mutation, no remaining activity when expressed as full length enzyme or as catalytic domain only in a deficient Dictyostelium discoideum cell line
D766A
-
site-directed mutagenesis of the central active site residue, inactive mutant
D766E
-
site-directed mutagenesis of the central active site residue, inactive mutant
D766S
-
site-directed mutagenesis of the central active site residue, inactive mutant
Q822R/Q823R/T825S
-
site-directed mutagenesis
R592A
-
site-directed mutagenesis of an alpha-kinase domain residue, the mutant shows 92% reduced activity compared to the wild-type enzyme
T825A
-
site-directed mutagenesis
T825E
-
site-directed mutagenesis
T825S
-
site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme
K645A
-
site-directed mutagenesis of an alpha-kinase domain residue, the mutant shows 98.5% reduced activity compared to the wild-type enzyme
additional information
-
the truncation mutant DELTAcoil-MHCK A comprising residues 1-498 is not affected in its autophosphorylation rate by F-actin
additional information
-
construction of single, double, and triple MHCK knockout cell lines concerning the 3 isozymes MHCK A, MHCK B, and MHCK C, the mutant cells defects in cytokinesis and myosin II overassembly increasing with the number of mutations, overview
additional information
-
overexpression of the RasGEF Q GEF domain activates RasB, causes enhanced recruitment of MHCK A to the cortex, and leads to cytokinesis defects in suspension phenocopying cells expressing constitutively active RasB, and myosin-null mutants, phenotype, overview. Cells overexpressing the GEF domain show at least 2fold higher levels of MHCK A associated with the cytoskeletal fractions
additional information
Q8MY12
version with deleted WD repeat domain: unable to phosphorylate myosin heavy chain to a significant level, phosphorylates MH-1 peptide
additional information
P90648
generation of the MHCKB truncation lacking only the WD-repeat domain and of a mutant lacking the N-rich region. Cells overexpressing the MHCK mutant lacking only the WD-repeat domain exhibit cytokinesis defects and decreased myosin II assembly
additional information
-
generation of a DELTA809 truncation mutant, phosphothreonine and the QQG(p)TMVMPD peptide restore the phosphorylation and also the ATPase activity of the mutant alpha-kinade domain, but mutations R734A and D762A abolish the ability of phosphothreonine to activate mutant alpha-kinase domain DELTA809