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FLASH GENE

Symbol

MYLK

contributors: mct - updated : 24-08-2017

HGNC name	myosin light chain kinase
HGNC id	7590

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Corresponding disease	MMIH3 megacystis-microcolon-intestinal hypoperistalsis syndrome 3 TAAD8 thoracic aortic aneurysm with aortic dissection 8
Location	3q21.1      Physical location : 123.331.144 - 123.603.149
Synonym name	smooth muscle myosin light chain kinase
	myosin, like chain kinase, Ca2+/calmodulin dependent, smooth muscle, non muscle MLC and KRP-related kinase (telokin) common gene
	myosin, light polypeptide kinase
	telokin
Synonym symbol(s)	MLCK, FLJ12216, KRP, MLCK108, MLCK210, MSTP083, MYLK1, MLCK1, DKFZp686I10125, smMLCK
EC.number	2.7.11.18, 2.7.11.8

DNA

TYPE	functioning gene
STRUCTURE	272.01 kb     34 Exon(s)

10 Kb 5' upstream gene genomic sequence study

regulatory sequence	Promoter
text structure	at least two promoters

MAPPING

cloned

Y

linked

N

status

confirmed

Map	cen - D3S1278 - D3S3529 - D3S3379 - D3S1558 - D3S3515 - D3S3513 - D3S3709 - D3S3576 - D3S1267 - D3S3645 - MYLK /D3S3552 - D3S3519 - D3S3646 - D3S1269 - D3S3569 - D3S1551 - qter

regionally located

not closely linked to olfactory receptor genes

RNA

TRANSCRIPTS	type	messenger

text	smooth muscle MLCK

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_053032 3 - 2679 NP_444260 - 154 - 2010 21055718 also called SM-MLCK or variant 8 NM_053025 34 - 7852 NP_444253 210.7 1914 . adult, fetal tissues, nervous system (neurons, glia) and liver, lung, kidney, brain (hippocampus, entorhinal and frontal cortex), eye, aortic tissue . limited to well differentiated enterocytes, and this expression correlates closely with development of Na(+)-nutrient cotransport-dependent tight junction . in developing human heart 2010 21055718 also called variant 1 or non muscle MLCK1 full lenght of NM-MLCK isoform responsible for tight junction regulation in absorptive enterocytes elevated hydrostatic pressure in glaucomas, increased the expression MYLK-210 in astrocytes NM_053031 3 - 2676 NP_444259 17 153 some smooth muscles, eye not in aorta, brain 2010 21055718 alsos called KRP or variant 7 encodes the shorter isoform of kinase related protein, telokin first exon corresponds to intron 30 and the remainder of the transcript corresponds to the last two exons of the gene elevated hydrostatic pressure in glaucomas, increased the expression MYLK-130 in astrocytes noncatalytic protein product that affects calcium sensitivity of contraction, primarily in intestinal smooth muscle NM_053026 33 - 7645 NP_444254 203.1 1845 adult, fetal tissues 2010 21055718 also called MLCK2 or variant 2 internal deletion NM_053027 33 - 7699 NP_444255 205.1 1863 adult, fetal tissues 2010 21055718 also called MLCK3a/b or variant 3A internal deletion does not utilize exon 30 NM_053028 32 - 7492 NP_444256 197.4 1794 adult, fetal tissues 2010 21055718 also called MLCK4 or variant 3B internal deletion does not utilize exons 11 and 30 NM_001321309 33 - 7644 NP_001308238 - 1738 - 2010 21055718 nmMLCK2 33 splicing - - - highly expressed in vascular endothelial cells (EC) 2017 27529643 lacking exon 11 associated with reduced EC barrier integrity

EXPRESSION

Type	ubiquitous

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Cardiovascular heart       highly Digestive esophagus       highly   intestine small intestine     highly Reproductive male system prostate     highly Respiratory respiratory tract trachea     highly

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Muscular striatum cardiac

cells

System Cell Pubmed Species Stage Rna symbol Muscular myocyte

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	N-terminus of the long MLCK inducing a disruption in normal spindle morphology and metaphase arrest
	three C2-type Ig-like domains
	a kinase domain
	a regulatory Ca2+ binding domains

HOMOLOGY

Homologene

FAMILY	protein kinase superfamily
	CAMK Ser/Thr protein kinase family

CATEGORY

enzyme

SUBCELLULAR LOCALIZATION	extracellular
	intracellular
	intracellular,cytoplasm,cytosolic
text	at the intercalated discs of cardiac myocytes

basic FUNCTION	perijunctional myosin light chain kinase, stimulating myosin ATPase activity without phosphorylating myosin light chain
	key enzyme in muscle contraction
	has an unexpected regulatory function during mitosis
	important kinase required for phosphorylation of the regulatory light chain (RLC) of myosin, leading to its activation and subsequent interaction with actin filaments
	activation of perijunctional myosin light chain kinase (MLCK) is sufficient to enhance paracellular permeability and is required for tight junction barrier regulation in response to Na+-nutrient cotransport, inflammatory cytokines, or pathogenic bacteria
	its activation is sufficient to enhance paracellular permeability and is required for tight junction barrier regulation in response to Na+-nutrient cotransport, inflammatory cytokines, or pathogenic bacteria
	is a key regulator involved in endothelial hyperpermeability, and IL1B has been shown to mediate MYLK-dependent barrier dysfunction in epithelia
	critical role in cell migration involves regulating the cell membrane tension and protrusion necessary for migration, thereby stabilizing the membrane skeleton through F-actin-binding activity
	plays a crucial role in artery contraction, which regulates blood pressure and blood flow distribution
	contributes to Ca(2+) flux regulation in vascular smooth muscle (VSM) and in non-muscle cells, where cytoskeleton has been suggested to help Ca(2+) channels trafficking
	likely is linked to timely blastocyst formation, though it is dispensable for oocyte meiotic maturation
	involved in isoform-specific non-muscle and smooth muscle contraction and regulation of vascular permeability during inflammation
	vital participant in regulating vascular barrier responses to mechanical and inflammatory stimuli
	key regulator of cell motility
	important kinase required for myosin activation and subsequent interaction with actin filaments

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component

INTERACTION

DNA

RNA

small molecule

protein	phosphorylating myosin light chain
	interacting with TJP1 (MYLK activity is critical to TJP1, but not claudin-1, occludin, or actin) exchange at the tight junction)
	CLDN2 regulates colorectal inflammation via MYLK
	FOXF1 directly binds to and activates the telokin (MYLK) promoter
	NFKB1 is a novel partner of MYLK within endothelial cells

cell & other

REGULATION

Other

Ca2+/calmodulin dependent

ASSOCIATED DISORDERS

corresponding disease(s)

TAAD8 , MMIH3

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional     --low   in aortic dissection

Susceptibility

to familial thoracic aortic aneurysms leading to acute aortic dissections to acute lung injury (ALI) and asthma

Variant & Polymorphism other	heterozygous loss-of-function mutations in MYLK are associated with aortic dissections
	SNPs (P21H, S147P, V261A) alter the N-terminal amino acid sequence of the non-muscle isoform of MLCK (nmMLCK) and are highly associated with susceptibility to acute lung injury (ALI) and asthma

Candidate gene
Marker	hypermethylated BRINP3 and MYLK can be used as potential biomarkers for diagnosis and pre-warning of gastric cancer
Therapy target
	System Type Disorder Pubmed neurosensorial visual anterior chamber may be a new target for intervention in glaucoma to alter reactive astrocyte migration in the optic nerve head

ANIMAL & CELL MODELS