Human Gene MYLK (ENST00000359169.5) Description and Page Index
  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. (from UniProt Q15746)
RefSeq Summary (NM_053027): 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].
Gencode Transcript: ENST00000359169.5
Gencode Gene: ENSG00000065534.18
Transcript (Including UTRs)
   Position: hg38 chr3:123,612,298-123,876,618 Size: 264,321 Total Exon Count: 32 Strand: -
Coding Region
   Position: hg38 chr3:123,614,105-123,793,841 Size: 179,737 Coding Exon Count: 30 

Page IndexSequence and LinksUniProtKB CommentsMalaCardsCTDRNA-Seq Expression
Microarray ExpressionRNA StructureProtein StructureOther SpeciesGO AnnotationsmRNA Descriptions
PathwaysOther NamesGeneReviewsMethods
Data last updated: 2019-09-04

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr3:123,612,298-123,876,618)mRNA (may differ from genome)Protein (1863 aa)
Gene SorterGenome BrowserOther Species FASTAGene interactionsTable SchemaBioGPS
CGAPEnsemblExonPrimerGeneCardsHGNCLynx
MGImyGene2neXtProtPubMedReactomeStanford SOURCE
UniProtKBWikipedia

-  Comments and Description Text from UniProtKB
  ID: MYLK_HUMAN
DESCRIPTION: RecName: Full=Myosin light chain kinase, smooth muscle; Short=MLCK; Short=smMLCK; EC=2.7.11.18; AltName: Full=Kinase-related protein; Short=KRP; AltName: Full=Telokin; Contains: RecName: Full=Myosin light chain kinase, smooth muscle, deglutamylated form;
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.
CATALYTIC ACTIVITY: ATP + [myosin light-chain] = ADP + [myosin light-chain] phosphate.
COFACTOR: Magnesium.
COFACTOR: Calcium.
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.
BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=6.5 uM for MLC (isoform 1 at 22 degrees Celsius); KM=7.2 uM for MLC (isoform 2 at 22 degrees Celsius); Vmax=11.9 umol/min/mg enzyme (isoform 1 at 22 degrees Celsius); Vmax=10.9 umol/min/mg enzyme (isoform 1 at 22 degrees Celsius);
SUBUNIT: All isoforms including Telokin bind calmodulin. Interacts with SVIL (By similarity). Interacts with CTTN; this interaction is reduced during thrombin-induced endothelial cell (EC) contraction but is promoted by the barrier-protective agonist sphingosine 1-phosphate (S1P) within lamellipodia. A complex made of ABL1, CTTN and MYLK regulates cortical actin-based cytoskeletal rearrangement critical to sphingosine 1-phosphate (S1P)-mediated endothelial cell (EC) barrier enhancement. Binds to NAA10/ARD1 and PTK2B/PYK2.
INTERACTION: P16333:NCK1; NbExp=2; IntAct=EBI-968482, EBI-389883;
SUBCELLULAR LOCATION: Cytoplasm. Cell projection, lamellipodium. Cleavage furrow. Cytoplasm, cytoskeleton. Note=Localized to stress fibers during interphase and to the cleavage furrow during mitosis.
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).
INDUCTION: Accumulates in individuals with asthma (at protein levels). Induced by tumor necrosis factor (TNF). Repressed by androgens (e.g. R1881).
PTM: Can probably be down-regulated by phosphorylation. Tyrosine phosphorylation by ABL1 increases kinase activity, reverses MLCK- mediated inhibition of Arp2/3-mediated actin polymerization, and enhances CTTN-binding. Phosphorylation by SRC at Tyr-464 and Tyr- 471 promotes CTTN binding.
PTM: The C-terminus is deglutamylated by AGTPBP1/ CCP1, AGBL1/CCP4 and AGBL4/CCP6, leading to the formation of Myosin light chain kinase, smooth muscle, deglutamylated form. The consequences of C- terminal deglutamylation are unknown (By similarity).
PTM: Acetylated at Lys-608 by NAA10/ARD1 via a calcium-dependent signaling; this acetylation represses kinase activity and reduces tumor cell migration.
DISEASE: Defects in MYLK are the cause of familial aortic aneurysm thoracic type 7 (AAT7) [MIM:613780]. AAT7 is 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.
MISCELLANEOUS: In asthmatic patients, overexpression promotes actin filament propulsion, thus contributing to airway hyperresponsiveness. Some MYLK variants may contribute to acute lung injury (ALI) susceptibility. Potential therapeutic target in the treatment of burn edema.
SIMILARITY: Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family.
SIMILARITY: Contains 1 fibronectin type-III domain.
SIMILARITY: Contains 9 Ig-like C2-type (immunoglobulin-like) domains.
SIMILARITY: Contains 1 protein kinase domain.
SEQUENCE CAUTION: Sequence=AAD15922.1; Type=Frameshift; Positions=1433; Sequence=AAD15923.1; Type=Frameshift; Positions=1433; Sequence=AAD15924.1; Type=Frameshift; Positions=1433;
WEB RESOURCE: Name=Wikipedia; Note=Myosin light-chain kinase entry; URL="http://en.wikipedia.org/wiki/Myosin_light-chain_kinase";

-  MalaCards Disease Associations
  MalaCards Gene Search: MYLK
Diseases sorted by gene-association score: aortic aneurysm, familial thoracic 7* (1230), mylk-related thoracic aortic aneurysms and aortic dissections* (500), aortic aneurysm (18), aneurysm (14), giardiasis (12), diabetic encephalopathy (5), fibromuscular dysplasia (5), aortic aneurysm, familial thoracic 1 (5), primary cutaneous amyloidosis (4), asthma (3)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 180.30 RPKM in Esophagus - Muscularis
Total median expression: 1509.34 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -52.60186-0.283 Picture PostScript Text
3' UTR -413.701807-0.229 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR003961 - Fibronectin_type3
IPR007110 - Ig-like
IPR013783 - Ig-like_fold
IPR013098 - Ig_I-set
IPR003599 - Ig_sub
IPR003598 - Ig_sub2
IPR011009 - Kinase-like_dom
IPR020675 - Myosin_light_ch_kinase-rel
IPR000719 - Prot_kinase_cat_dom
IPR017441 - Protein_kinase_ATP_BS
IPR002290 - Ser/Thr_dual-sp_kinase_dom
IPR008271 - Ser/Thr_kinase_AS

Pfam Domains:
PF00041 - Fibronectin type III domain
PF07679 - Immunoglobulin I-set domain
PF00069 - Protein kinase domain

Protein Data Bank (PDB) 3-D Structure
MuPIT help

2CQV
- NMR MuPIT

2K0F
- NMR MuPIT

2YR3
- NMR MuPIT


ModBase Predicted Comparative 3D Structure on Q15746
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-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
Genome BrowserGenome BrowserNo orthologNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     
MGIRGD    
Protein SequenceProtein Sequence    
AlignmentAlignment    

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0000166 nucleotide binding
GO:0003779 actin binding
GO:0004672 protein kinase activity
GO:0004674 protein serine/threonine kinase activity
GO:0004687 myosin light chain kinase activity
GO:0005515 protein binding
GO:0005516 calmodulin binding
GO:0005524 ATP binding
GO:0016301 kinase activity
GO:0016740 transferase activity
GO:0046872 metal ion binding

Biological Process:
GO:0006468 protein phosphorylation
GO:0006936 muscle contraction
GO:0006939 smooth muscle contraction
GO:0014820 tonic smooth muscle contraction
GO:0016310 phosphorylation
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:0005856 cytoskeleton
GO:0005886 plasma membrane
GO:0015629 actin cytoskeleton
GO:0030027 lamellipodium
GO:0032154 cleavage furrow
GO:0042995 cell projection


-  Descriptions from all associated GenBank mRNAs
  LF385123 - JP 2014500723-A/192626: Polycomb-Associated Non-Coding RNAs.
MA620700 - JP 2018138019-A/192626: Polycomb-Associated Non-Coding RNAs.
BC064695 - Homo sapiens myosin, light polypeptide kinase, mRNA (cDNA clone IMAGE:30346535), partial cds.
AF069601 - Homo sapiens myosin light chain kinase isoform 2 (MLCK) mRNA, complete cds.
AF069602 - Homo sapiens myosin light chain kinase isoform 3A (MLCK) mRNA, complete cds.
AF069603 - Homo sapiens myosin light chain kinase isoform 3B (MLCK) mRNA, complete cds.
U48959 - Homo sapiens myosin light chain kinase (MLCK) mRNA, complete cds.
AY424269 - Homo sapiens myosin light chain polypeptide kinase isoform 2 (MYLK) mRNA, complete cds, alternatively spliced.
AY424270 - Homo sapiens myosin lignt chain polypeptide kinase isoform 1 (MYLK) mRNA, complete cds, alternatively spliced.
AY339601 - Homo sapiens long myosin light chain kinase mRNA, complete cds.
AB384705 - Synthetic construct DNA, clone: pF1KB1487, Homo sapiens MYLK gene for myosin light chain kinase, complete cds, without stop codon, in Flexi system.
AK311053 - Homo sapiens cDNA, FLJ18095.
AK022278 - Homo sapiens cDNA FLJ12216 fis, clone MAMMA1001038, highly similar to MYOSIN LIGHT CHAIN KINASE, SMOOTH MUSCLE AND NON-MUSCLE ISOZYMES (EC 2.7.1.117).
AL833897 - Homo sapiens mRNA; cDNA DKFZp761O211 (from clone DKFZp761O211).
BC064420 - Homo sapiens myosin light chain kinase, mRNA (cDNA clone IMAGE:5751596), complete cds.
AF172084 - Homo sapiens MSTP083 mRNA, complete cds.
AK127437 - Homo sapiens cDNA FLJ45529 fis, clone BRTHA2027546.
AK025953 - Homo sapiens cDNA: FLJ22300 fis, clone HRC04759.
CR749364 - Homo sapiens mRNA; cDNA DKFZp686I10125 (from clone DKFZp686I10125).
BC015838 - Homo sapiens cDNA clone IMAGE:4296556.
BC062755 - Homo sapiens cDNA clone IMAGE:4043774, partial cds.
BC113456 - Homo sapiens myosin light chain kinase, mRNA (cDNA clone IMAGE:8322508), partial cds.
BC113458 - Homo sapiens myosin light chain kinase, mRNA (cDNA clone IMAGE:8322510), partial cds.
BC107783 - Homo sapiens myosin light chain kinase, mRNA (cDNA clone IMAGE:6668966), partial cds.
LF339079 - JP 2014500723-A/146582: Polycomb-Associated Non-Coding RNAs.
MA574656 - JP 2018138019-A/146582: Polycomb-Associated Non-Coding RNAs.
LF339078 - JP 2014500723-A/146581: Polycomb-Associated Non-Coding RNAs.
MA574655 - JP 2018138019-A/146581: Polycomb-Associated Non-Coding RNAs.
BC100761 - Homo sapiens myosin light chain kinase, mRNA (cDNA clone IMAGE:40000097), complete cds.
BC100762 - Homo sapiens myosin light chain kinase, mRNA (cDNA clone IMAGE:40000098), complete cds.
BC100763 - Homo sapiens myosin light chain kinase, mRNA (cDNA clone IMAGE:40000099), complete cds.
JD091129 - Sequence 72153 from Patent EP1572962.
BC034911 - Homo sapiens cDNA clone IMAGE:5275648, containing frame-shift errors.
AB037663 - Homo sapiens MLCK mRNA for myosin light chain kinase, complete cds.
X85337 - H.sapiens mRNA for myosin light chain kinase.
JD091128 - Sequence 72152 from Patent EP1572962.
JD091127 - Sequence 72151 from Patent EP1572962.
AK300610 - Homo sapiens cDNA FLJ53659 complete cds, highly similar to Myosin light chain kinase, smooth muscle (EC2.7.11.18).
AF069604 - Homo sapiens myosin light chain kinase isoform 4 (MLCK) mRNA, partial cds.
X90870 - H.sapiens mRNA for myosin light chain kinase.
AF096773 - Homo sapiens kinase-related protein mRNA, complete cds.
AF096774 - Homo sapiens kinase-related protein isoform 1 mRNA, complete cds.
AF096775 - Homo sapiens kinase-related protein isoform 2 mRNA, complete cds.
JD469167 - Sequence 450191 from Patent EP1572962.
JD214684 - Sequence 195708 from Patent EP1572962.
AK314412 - Homo sapiens cDNA, FLJ95192, Homo sapiens myosin, light polypeptide kinase (MYLK), transcriptvariant 7, mRNA.
AK314443 - Homo sapiens cDNA, FLJ95241, Homo sapiens myosin, light polypeptide kinase (MYLK), transcriptvariant 8, mRNA.
BC017811 - Homo sapiens myosin light chain kinase, mRNA (cDNA clone IMAGE:4296486), partial cds.
LF339077 - JP 2014500723-A/146580: Polycomb-Associated Non-Coding RNAs.
MA574654 - JP 2018138019-A/146580: Polycomb-Associated Non-Coding RNAs.
LF339076 - JP 2014500723-A/146579: Polycomb-Associated Non-Coding RNAs.
MA574653 - JP 2018138019-A/146579: Polycomb-Associated Non-Coding RNAs.
AL832211 - Homo sapiens mRNA; cDNA DKFZp686N112 (from clone DKFZp686N112).
Y09530 - H.sapiens mRNA for telokin.
JD482855 - Sequence 463879 from Patent EP1572962.
BC040115 - Homo sapiens, Similar to myosin, light polypeptide kinase, clone IMAGE:5539579, mRNA.
JD371928 - Sequence 352952 from Patent EP1572962.
JD134923 - Sequence 115947 from Patent EP1572962.
JD374310 - Sequence 355334 from Patent EP1572962.
KX603653 - Homo sapiens microRNA-29a miRNA, complete sequence.
DQ642692 - Homo sapiens long myosin light chain kinase (MYLK) mRNA, partial cds.
DQ642691 - Homo sapiens long myosin light chain kinase (MYLK) mRNA, partial cds.
JD395221 - Sequence 376245 from Patent EP1572962.
JD443238 - Sequence 424262 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa04020 - Calcium signaling pathway
hsa04270 - Vascular smooth muscle contraction
hsa04510 - Focal adhesion
hsa04810 - Regulation of actin cytoskeleton

Reactome (by CSHL, EBI, and GO)

Protein Q15746 (Reactome details) participates in the following event(s):

R-HSA-445797 MYLK (MLCK) Active Calmodulin Binding
R-HSA-5668984 PAK1 or PAK2 phosphorylates MYLK
R-HSA-445813 Phosphorylation of Smooth Muscle Myosin Light Chains
R-HSA-5668978 MYLK (MLCK) phosphorylates MRLCs of the non-muscle myosin II complex
R-HSA-445355 Smooth Muscle Contraction
R-HSA-5627123 RHO GTPases activate PAKs
R-HSA-397014 Muscle contraction
R-HSA-195258 RHO GTPase Effectors
R-HSA-194315 Signaling by Rho GTPases
R-HSA-162582 Signal Transduction

-  Other Names for This Gene
  Alternate Gene Symbols: MLCK, MLCK1, MYLK1, MYLK_HUMAN, O95796, O95797, O95798, O95799, Q14844, Q15746, Q16794, Q3ZCP9, Q5MY99, Q5MYA0, Q7Z4J0, Q9C0L5, Q9UBG5, Q9UBY6, Q9UIT9, U48959, uc062ncq.1
UCSC ID: uc062ncq.1
RefSeq Accession: NM_053027
Protein: Q15746 (aka MYLK_HUMAN or KMLS_HUMAN)
CCDS: CCDS3023.1, CCDS43141.1, CCDS46896.1

-  GeneReviews for This Gene
  GeneReviews article(s) related to gene MYLK:
taa (Heritable Thoracic Aortic Disease Overview)

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.