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  3. MYLK

MYLK (Myosin light chain kinase)

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Summary of MYLK

The gene codes for a protein, myosin light chain kinase. It codes for both smooth muscle and nonmuscle [R].

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The Function of MYLK

Calcium/calmodulin-dependent myosin light chain kinase implicated in smooth muscle contraction via phosphorylation of myosin light chains (MLC). Also regulates actin-myosin interaction through a non-kinase activity. Phosphorylates PTK2B/PYK2 and myosin light-chains. Involved in the inflammatory response (e.g. apoptosis, vascular permeability, leukocyte diapedesis), cell motility and morphology, airway hyperreactivity and other activities relevant to asthma. Required for tonic airway smooth muscle contraction that is necessary for physiological and asthmatic airway resistance. Necessary for gastrointestinal motility. Implicated in the regulation of endothelial as well as vascular permeability, probably via the regulation of cytoskeletal rearrangements. In the nervous system it has been shown to control the growth initiation of astrocytic processes in culture and to participate in transmitter release at synapses formed between cultured sympathetic ganglion cells. Critical participant in signaling sequences that result in fibroblast apoptosis. Plays a role in the regulation of epithelial cell survival. Required for epithelial wound healing, especially during actomyosin ring contraction during purse-string wound closure. Mediates RhoA-dependent membrane blebbing. Triggers TRPC5 channel activity in a calcium-dependent signaling, by inducing its subcellular localization at the plasma membrane. Promotes cell migration (including tumor cells) and tumor metastasis. PTK2B/PYK2 activation by phosphorylation mediates ITGB2 activation and is thus essential to trigger neutrophil transmigration during acute lung injury (ALI). May regulate optic nerve head astrocyte migration. Probably involved in mitotic cytoskeletal regulation. Regulates tight junction probably by modulating ZO-1 exchange in the perijunctional actomyosin ring. Mediates burn-induced microvascular barrier injury; triggers endothelial contraction in the development of microvascular hyperpermeability by phosphorylating MLC. Essential for intestinal barrier dysfunction. Mediates Giardia spp.-mediated reduced epithelial barrier function during giardiasis intestinal infection via reorganization of cytoskeletal F-actin and tight junctional ZO-1. Necessary for hypotonicity-induced Ca(2+) entry and subsequent activation of volume-sensitive organic osmolyte/anion channels (VSOAC) in cervical cancer cells. Responsible for high proliferative ability of breast cancer cells through anti-apoptosis.

Protein names

Recommended name:

Myosin light chain kinase, smooth muscle

Short name:

KRP

Alternative name(s):

MLCK
smMLCK
Kinase-related protein
Telokin

MYLK SNPs

    To see your genotype, you should be logged in and have a file with your genotype uploaded.

  1. RS820336 (MYLK) ??

Top Gene-Substance Interactions

MYLK Interacts with These Diseases

Disease Score

Substances That Increase MYLK

Substances Interaction Organism Category

Substances That Decrease MYLK

Substances Interaction Organism Category

Advanced Summary

     Covered on Genetics Home Reference: familial thoracic aortic aneurysm and dissectionFrom NCBI Gene: Aortic aneurysm, familial thoracic 7From UniProt: Aortic aneurysm, familial thoracic 7 (AAT7): A disease characterized by permanent dilation of the thoracic aorta usually due to degenerative changes in the aortic wall. It is primarily associated with a characteristic histologic appearance known as 'medial necrosis' or 'Erdheim cystic medial necrosis' in which there is degeneration and fragmentation of elastic fibers, loss of smooth muscle cells, and an accumulation of basophilic ground substance. [MIM:613780]

     From NCBI Gene: This gene, a muscle member of the immunoglobulin gene superfamily, encodes myosin light chain kinase which is a calcium/calmodulin dependent enzyme. This kinase phosphorylates myosin regulatory light chains to facilitate myosin interaction with actin filaments to produce contractile activity. This gene encodes both smooth muscle and nonmuscle isoforms. In addition, using a separate promoter in an intron in the 3' region, it encodes telokin, a small protein identical in sequence to the C-terminus of myosin light chain kinase, that is independently expressed in smooth muscle and functions to stabilize unphosphorylated myosin filaments. A pseudogene is located on the p arm of chromosome 3. Four transcript variants that produce four isoforms of the calcium/calmodulin dependent enzyme have been identified as well as two transcripts that produce two isoforms of telokin. Additional variants have been identified but lack full length transcripts. [provided by RefSeq, Jul 2008] From UniProt: Calcium/calmodulin-dependent myosin light chain kinase implicated in smooth muscle contraction via phosphorylation of myosin light chains (MLC). Also regulates actin-myosin interaction through a non-kinase activity. Phosphorylates PTK2B/PYK2 and myosin light-chains. Involved in the inflammatory response (e.g. apoptosis, vascular permeability, leukocyte diapedesis), cell motility and morphology, airway hyperreactivity and other activities relevant to asthma. Required for tonic airway smooth muscle contraction that is necessary for physiological and asthmatic airway resistance. Necessary for gastrointestinal motility. Implicated in the regulation of endothelial as well as vascular permeability, probably via the regulation of cytoskeletal rearrangements. In the nervous system it has been shown to control the growth initiation of astrocytic processes in culture and to participate in transmitter release at synapses formed between cultured sympathetic ganglion cells. Critical participant in signaling sequences that result in fibroblast apoptosis. Plays a role in the regulation of epithelial cell survival. Required for epithelial wound healing, especially during actomyosin ring contraction during purse-string wound closure. Mediates RhoA-dependent membrane blebbing. Triggers TRPC5 channel activity in a calcium-dependent signaling, by inducing its subcellular localization at the plasma membrane. Promotes cell migration (including tumor cells) and tumor metastasis. PTK2B/PYK2 activation by phosphorylation mediates ITGB2 activation and is thus essential to trigger neutrophil transmigration during acute lung injury (ALI). May regulate optic nerve head astrocyte migration. Probably involved in mitotic cytoskeletal regulation. Regulates tight junction probably by modulating ZO-1 exchange in the perijunctional actomyosin ring. Mediates burn-induced microvascular barrier injury; triggers endothelial contraction in the development of microvascular hyperpermeability by phosphorylating MLC. Essential for intestinal barrier dysfunction. Mediates Giardia spp.-mediated reduced epithelial barrier function during giardiasis intestinal infection via reorganization of cytoskeletal F-actin and tight junctional ZO-1. Necessary for hypotonicity-induced Ca(2+) entry and subsequent activation of volume-sensitive organic osmolyte/anion channels (VSOAC) in cervical cancer cells. Responsible for high proliferative ability of breast cancer cells through anti-apoptosis.

Conditions with Increased Gene Activity

Condition Change (log2fold) Comparison Species Experimental variables Experiment name

Conditions with Decreased Gene Activity

Condition Change (log2fold) Comparison Species Experimental variables Experiment name

Technical

The following transcription factors affect gene expression:

  • PPAR-gamma1

Tissue specificity:

Smooth muscle and non-muscle isozymes are expressed in a wide variety of adult and fetal tissues and in cultured endothelium with qualitative expression appearing to be neither tissue- nor development-specific. Non-muscle isoform 2 is the dominant splice variant expressed in various tissues. Telokin has been found in a wide variety of adult and fetal tissues. Accumulates in well differentiated enterocytes of the intestinal epithelium in response to tumor necrosis factor (TNF).

Gene Pathways:

  • Regulation of actin cytoskeleton
  • Calcium signaling pathway
  • Vascular smooth muscle contraction
  • Gastric acid secretion
  • Muscle contraction

Induction:

Accumulates in individuals with asthma (at protein levels). Induced by tumor necrosis factor (TNF). Repressed by androgens (e.g. R1881).

Enzyme Regulation:

Isoform 1 is activated by phosphorylation on Tyr-464 and Tyr-471. Isoforms which lack these tyrosine residues are not regulated in this way. All catalytically active isoforms require binding to calcium and calmodulin for activation. Repressed by organometallic pyridylnaphthalimide complexes, wortmannin, ML-7 (a synthetic naphthalenesulphonyl derivative that inhibits the binding of ATP to MLCK) and ML-9.

Molecular Function:

  • Atp Binding
  • Metal Ion Binding
  • Myosin Light Chain Kinase Activity

Biological Processes:

  • Aorta Smooth Muscle Tissue Morphogenesis
  • Bleb Assembly
  • Cellular Hypotonic Response
  • Muscle Contraction
  • Positive Regulation Of Calcium Ion Transport
  • Positive Regulation Of Cell Migration
  • Positive Regulation Of Wound Healing
  • Protein Phosphorylation
  • Smooth Muscle Contraction
  • Tonic Smooth Muscle Contraction
  • Mitophagy In Response To Mitochondrial Depolarization
  • Positive Regulation Of Defense Response To Virus By Host
  • Xenophagy
*synonyms

Synonyms/Aliases/Alternative Names of the Gene:

hypothetical protein| A306_12146| AAT7| Anapl_00914| AS28_05510| CB1_001278010| CCDC14| coiled-coil domain containing 14| D623_10032652| GW7_19694| H920_00254| I79_000661| kinase related protein| kinase-related protein| kinase related protein, telokin| KRP| M91_04245| M959_07018| MDA_GLEAN10007519| Mlck| MLCK1| MLCK108| mlck210| MSTP083| MYLK1| Myosin light chain kinase, smooth muscle| myosin, light polypeptide kinase| N300_03632| N301_09548| N302_02342| N303_12764| N307_04442| N308_15950| N312_13256| N320_01737| N321_11180| N322_12776| N324_12414| N326_13056| N329_06365| N330_05773| N333_12851| N339_01568| N340_13678| N341_03118| nmMlck| PAL_GLEAN10006555| PANDA_011597| SMMLCK| smooth muscle myosin light chain kinase| smooth muscle myosin light chain kinase (61-kDa active fragment)| telokin| TREES_T100009179| Y1Q_013967| Y956_05771| Z169_07869| mylk

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