InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: MYLK

Summary

InnateDB Protein

IDBP-476347.4

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

MYLK

Protein Name

myosin light chain kinase

Synonyms

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

Species

Homo sapiens

Ensembl Protein

ENSP00000428967

InnateDB Gene

IDBG-53043 (MYLK)

Protein Structure

UniProt Annotation

Function

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. {ECO:0000269PubMed:11113114, ECO:0000269PubMed:11976941, ECO:0000269PubMed:15020676, ECO:0000269PubMed:15825080, ECO:0000269PubMed:16284075, ECO:0000269PubMed:16723733, ECO:0000269PubMed:18587400, ECO:0000269PubMed:18710790, ECO:0000269PubMed:19826488, ECO:0000269PubMed:20139351, ECO:0000269PubMed:20181817, ECO:0000269PubMed:20375339, ECO:0000269PubMed:20453870}.

Subcellular Localization

Cytoplasm. Cell projection, lamellipodium. Cleavage furrow. Cytoplasm, cytoskeleton. Note=Localized to stress fibers during interphase and to the cleavage furrow during mitosis.

Disease Associations

Aortic aneurysm, familial thoracic 7 (AAT7) [MIM:613780]: 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. {ECO:0000269PubMed:21055718}. Note=The disease is caused by mutations affecting the gene represented in this entry.

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). {ECO:0000269PubMed:10536370, ECO:0000269PubMed:16835238, ECO:0000269PubMed:20053363, ECO:0000269PubMed:8575746}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 24 experimentally validated interaction(s) in this database.

Experimentally validated
Total	24 [view]
Protein-Protein	22 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	2 [view]
RNA-RNA	0
DNA-RNA	0

Gene Ontology

Molecular Function

Accession	GO Term
GO:0003779	actin binding
GO:0004683	calmodulin-dependent protein kinase activity
GO:0004687	myosin light chain kinase activity
GO:0005515	protein binding
GO:0005516	calmodulin binding
GO:0005524	ATP binding
GO:0046872	metal ion binding

Biological Process

GO:0006468	protein phosphorylation
GO:0006936	muscle contraction
GO:0006939	smooth muscle contraction
GO:0007015	actin filament organization
GO:0014820	tonic smooth muscle contraction
GO:0030335	positive regulation of cell migration
GO:0032060	bleb assembly
GO:0051928	positive regulation of calcium ion transport
GO:0060414	aorta smooth muscle tissue morphogenesis
GO:0071476	cellular hypotonic response
GO:0090303	positive regulation of wound healing

Cellular Component

GO:0001725	stress fiber
GO:0005737	cytoplasm
GO:0005829	cytosol
GO:0030027	lamellipodium
GO:0032154	cleavage furrow
GO:0070062	extracellular vesicular exosome

Protein Structure and Domains

PDB ID

InterPro

IPR003598 Immunoglobulin subtype 2
IPR003599 Immunoglobulin subtype
IPR007110 Immunoglobulin-like domain
IPR013098 Immunoglobulin I-set
IPR013151 Immunoglobulin

PFAM

PF07679
PF00047

PRINTS

PIRSF

SMART

SM00408
SM00409

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt

Q15746