Literature summary for 2.7.11.18 extracted from

Shen, K.; Ramirez, B.; Mapes, B.; Shen, G.R.; Gokhale, V.; Brown, M.E.; Santarsiero, B.; Ishii, Y.; Dudek, S.M.; Wang, T.; Garcia, J.G.
Structure-function analysis of the non-muscle myosin light chain kinase (nmMLCK) isoform by NMR spectroscopy and molecular modeling: influence of MYLK variants (2015), PLoS ONE, 10, e0130515.

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Activating Compound

Activating Compound	Comment	Organism	Structure
additional information	pp60src- or c-Abl-mediated phosphorylation of nmMLCK at Y464 and Y471 increases MLC kinase activity	Homo sapiens

Cloned(Commentary)

Cloned (Comment)	Organism
two major nmMLCK splice variants, nmMLCK1 (about 211 kDa) and nmMLCK2 (about 203 kDa), differ by 69 amino acids within exon 11 (partially deleted in nmMLCK2), a stretch that contains the highly phosphorylated Y464 and Y471. Recombinant expression of wild-type and mutant isozymes nmMLCK1 in Escherichia coli strain BL21(DE3), recombinant expression of Flag-tagged nmMLCK1, recombinant expression of two variants of the 1-494aa segments, wild type (P21-S147-V261)-1-494-biotin and a single SNP (P147)-1-494-biotin	Homo sapiens

Cloned (Comment)

Organism

two major nmMLCK splice variants, nmMLCK1 (about 211 kDa) and nmMLCK2 (about 203 kDa), differ by 69 amino acids within exon 11 (partially deleted in nmMLCK2), a stretch that contains the highly phosphorylated Y464 and Y471. Recombinant expression of wild-type and mutant isozymes nmMLCK1 in Escherichia coli strain BL21(DE3), recombinant expression of Flag-tagged nmMLCK1, recombinant expression of two variants of the 1-494aa segments, wild type (P21-S147-V261)-1-494-biotin and a single SNP (P147)-1-494-biotin

Homo sapiens

Protein Variants

Protein Variants	Comment	Organism
P21H	site-directed mutagenesis, alters the N-terminal amino acid sequence of the non-muscle isoform of MLCK (nmMLCK) and is highly associated with susceptibility to acute lung injury and asthma, especially in individuals of African descent, the mutation causes minimal conformational changes compared to the wild-type enzyme	Homo sapiens
S147P	site-directed mutagenesis, alters the N-terminal amino acid sequence of the non-muscle isoform of MLCK (nmMLCK) and is highly associated with susceptibility to acute lung injury and asthma, especially in individuals of African descent, the mutation causes minimal conformational changes compared to the wild-type enzyme	Homo sapiens
V261A	site-directed mutagenesis, alters the N-terminal amino acid sequence of the non-muscle isoform of MLCK (nmMLCK) and is highly associated with susceptibility to acute lung injury and asthma, especially in individuals of African descent, the mutation causes minimal conformational changes compared to the wild-type enzyme	Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates	Organism	Comment (Nat. Sub.)	Natural Products	Comment (Nat. Pro.)	Rev.	Reac.
additional information	Homo sapiens	14-3-3 binding of nmMLCK	?	-	?

Organism

Organism	UniProt	Comment	Textmining
Homo sapiens	-	-	-

Posttranslational Modification

Posttranslational Modification	Comment	Organism
phosphoprotein	reversible Ser/Thr and Tyr nmMLCK phosphorylation contributes to differential regulation of enzymatic activity and cellular spatial targeting of the kinase. cAMP-dependent protein kinase A (PKA)-mediated phosphorylation of nmMLCK exerts paradoxical effects on kinase activity depending on whether the Ser/Thr phosphorylation sites resides within the unique nmMLCK N-terminus, the putative Src homology (SH) 3-binding sequences, or the calcium/calmodulin binding region. Tyr phosphorylation of nmMLCK by pp60src or c-Abl occurs during barrier disruption, during recovery, as well as following exposure to barrier enhancing stimuli. pp60src- or c-Abl-mediated phosphorylation of nmMLCK at Y464 and Y471 increases MLC kinase activity. The two major nmMLCK splice variants, nmMLCK1 (about 211 kDa) and nmMLCK2 (about 203 kDa), differ by 69 amino acids within exon 11 (partially deleted in nmMLCK2), a stretch that contains the highly phosphorylated Y464 and Y471, suggesting that nmMLCK splice variants are differentially regulated by Tyr phosphorylation	Homo sapiens

Purification (Commentary)

Purification (Comment)	Organism
recombinant wild-type and mutant isozymes nmMLCK1 from Escherichia coli strain BL21(DE3) by chromatography on a chitin column and dialysis	Homo sapiens

Source Tissue

Source Tissue	Comment	Organism	Textmining
additional information	non-muscle isozyme	Homo sapiens	-

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.	Reac.
additional information	14-3-3 binding of nmMLCK	Homo sapiens	?	-	?

Subunits

Subunits	Comment	Organism
More	structure-function analysis of the non-muscle myosin light chain kinase (nmMLCK) isoform by NMR spectroscopy and molecular modeling, overview	Homo sapiens

Synonyms

Synonyms	Comment	Organism
nmMLCK	-	Homo sapiens
non-muscle myosin light chain kinase	-	Homo sapiens

General Information

General Information	Comment	Organism
malfunction	non-muscle myosin light chain kinase (nmMLCK) mutations P21H, S147P, and V261A (all located to loops that connect the immunoglobulin-like domains of nmMLCK) alter the enzyme conformation and the N-terminal amino acid sequence of the non-muscle isoform of MLCK and are highly associated with susceptibility to acute lung injury and asthma, especially in individuals of African descent	Homo sapiens
additional information	structure-function analysis of the non-muscle myosin light chain kinase (nmMLCK) isoform by NMR spectroscopy and molecular modeling, overview. The two major nmMLCK splice variants, nmMLCK1 (about 211 kDa) and nmMLCK2 (about 203 kDa), differ by 69 amino acids within exon 11 (partially deleted in nmMLCK2), a stretch that contains the highly phosphorylated Y464 and Y471, suggesting that nmMLCK splice variants are differentially regulated by Tyr phosphorylation. Potential involvement of S147P and P21H SNP sites in nmMLCK1 in phosphorylation-dependent binding of 14-3-3 proteins	Homo sapiens
physiological function	the MYLK gene encodes the multifunctional enzyme, myosin light chain kinase (MLCK), involved in isoform-specific non-muscle and smooth muscle contraction and regulation of vascular permeability during inflammation. Reversible Ser/Thr and Tyr nmMLCK phosphorylation contributes to differential regulation of enzymatic activity and cellular spatial targeting of the kinase. Inhibition of Tyr phosphatase activities results in significant accumulation of pTyr-containing nmMLCK, increased MLC kinase activity, endothelial cell contraction and barrier dysfunction. nmMLCK regulation by reversible Tyr phosphorylation, overview. The N-terminal SH2 and SH3 domain-binding motifs (including an SH2-binding motif containing phosphorylated Y464) regulate nmMLCK interactions with other cytoskeletal regulatory proteins	Homo sapiens