Tchem MYLK Myosin light chain kinase, smooth muscle

Protein Summary

Description

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. 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]

Uniprot Accession IDs

• Q15746
• B4DUE3
• D3DN97
• O95796
• O95797
• O95798
• O95799
• Q14844
• Q16794
• Q17S15
• Q3ZCP9
• Q5MY99
• Q5MYA0
• Q6P2N0
• Q7Z4J0
• Q9C0L5
• Q9UBG5
• Q9UBY6
• Q9UIT9
• MLCK

Gene Name

• MYLK

Ensembl ID

• ENST00000346322
• ENSP00000320622
• ENSG00000065534
• ENST00000354792
• ENSP00000346846
• ENST00000359169
• ENSP00000352088
• ENST00000360304
• ENSP00000353452
• ENST00000360772
• ENSP00000354004
• ENST00000418370
• ENSP00000428967
• ENST00000475616
• ENSP00000418335
• ENST00000578202
• ENSP00000463691
• ENST00000583087
• ENSP00000462118

Symbol

• MLCK
• MLCK1
• MYLK1
• KRP
• AAT7
• MLCK
• MLCK1
• MYLK1
• smMLCK
• MLCK108
• MLCK210
• MSTP083

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
protein domain	1
molecular function	0.98
kinase	0.97
kinase perturbation	0.96
transcription factor perturbation	0.96

Protein Classes

DTO Classes

Protein / Kinase / Protein Kinase / Camk Group / Mlck Family / Myosin Light Chain Kinase, Smooth Muscle

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 1100.66   (req: < 5)

Gene RIFs: 98   (req: <= 3)

Antibodies: 328   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 1100.66   (req: >= 5)

Gene RIFs: 98   (req: > 3)

Antibodies: 328   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 17

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligands: 9

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 1