{"results":[{"entryType":"UniProtKB reviewed (Swiss-Prot)","primaryAccession":"Q15746","secondaryAccessions":["B4DUE3","D3DN97","O95796","O95797","O95798","O95799","Q14844","Q16794","Q17S15","Q3ZCP9","Q5MY99","Q5MYA0","Q6P2N0","Q7Z4J0","Q9C0L5","Q9UBG5","Q9UBY6","Q9UIT9"],"uniProtkbId":"MYLK_HUMAN","entryAudit":{"firstPublicDate":"1998-07-15","lastAnnotationUpdateDate":"2026-09-02","lastSequenceUpdateDate":"2010-07-13","entryVersion":244,"sequenceVersion":4},"annotationScore":5.0,"organism":{"scientificName":"Homo sapiens","commonName":"Human","taxonId":9606,"lineage":["Eukaryota","Metazoa","Chordata","Craniata","Vertebrata","Euteleostomi","Mammalia","Eutheria","Euarchontoglires","Primates","Haplorrhini","Catarrhini","Hominidae","Homo"]},"proteinExistence":"1: Evidence at protein level","proteinDescription":{"recommendedName":{"fullName":{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"Myosin light chain kinase, smooth muscle"},"shortNames":[{"value":"MLCK"},{"value":"smMLCK"}],"ecNumbers":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11113114"}],"value":"2.7.11.18"}]},"alternativeNames":[{"fullName":{"value":"Kinase-related protein"},"shortNames":[{"value":"KRP"}]},{"fullName":{"value":"Telokin"}}],"contains":[{"recommendedName":{"fullName":{"value":"Myosin light chain kinase, smooth muscle, deglutamylated form"}}}]},"genes":[{"geneName":{"evidences":[{"evidenceCode":"ECO:0000312","source":"HGNC","id":"HGNC:7590"}],"value":"MYLK"},"synonyms":[{"value":"MLCK"},{"value":"MLCK1"},{"value":"MYLK1"}]}],"comments":[{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q6PDN3"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11113114"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11976941"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15020676"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15825080"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16284075"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16723733"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18587400"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18710790"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19826488"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20139351"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20181817"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20375339"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20453870"}],"value":"Calcium/calmodulin-dependent myosin light chain kinase implicated in smooth muscle contraction via phosphorylation of myosin light chains (MLC) (PubMed:11113114). Also regulates actin-myosin interaction through a non-kinase activity (PubMed:11113114). Phosphorylates PTK2B/PYK2 and myosin light-chains (PubMed:11113114, PubMed:18587400). Involved in the inflammatory response (e.g. apoptosis, vascular permeability, leukocyte diapedesis), cell motility and morphology, airway hyperreactivity and other activities relevant to asthma (PubMed:20139351). Required for tonic airway smooth muscle contraction that is necessary for physiological and asthmatic airway resistance (By similarity). Necessary for gastrointestinal motility (By similarity). Implicated in the regulation of endothelial as well as vascular permeability, probably via the regulation of cytoskeletal rearrangements (By similarity). 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 (PubMed:20375339). Critical participant in signaling sequences that result in fibroblast apoptosis (PubMed:20453870). Plays a role in the regulation of epithelial cell survival (PubMed:16723733). Required for epithelial wound healing, especially during actomyosin ring contraction during purse-string wound closure (PubMed:15825080). Mediates RhoA-dependent membrane blebbing (PubMed:20181817). Triggers TRPC5 channel activity in a calcium-dependent signaling, by inducing its subcellular localization at the plasma membrane (PubMed:16284075). Promotes cell migration (including tumor cells) and tumor metastasis (PubMed:18710790, PubMed:19826488). PTK2B/PYK2 activation by phosphorylation mediates ITGB2 activation and is thus essential to trigger neutrophil transmigration during acute lung injury (ALI) (PubMed:18587400). May regulate optic nerve head astrocyte migration (PubMed:20375339). Probably involved in mitotic cytoskeletal regulation (PubMed:15020676). Regulates tight junction probably by modulating ZO-1 exchange in the perijunctional actomyosin ring (By similarity). Mediates burn-induced microvascular barrier injury; triggers endothelial contraction in the development of microvascular hyperpermeability by phosphorylating MLC (By similarity). Essential for intestinal barrier dysfunction (By similarity). Mediates Giardia spp.-mediated reduced epithelial barrier function during giardiasis intestinal infection via reorganization of cytoskeletal F-actin and tight junctional ZO-1 (By similarity). Necessary for hypotonicity-induced Ca(2+) entry and subsequent activation of volume-sensitive organic osmolyte/anion channels (VSOAC) in cervical cancer cells (PubMed:11976941). Responsible for high proliferative ability of breast cancer cells through anti-apoptosis (PubMed:20453870)"}],"commentType":"FUNCTION"},{"commentType":"CATALYTIC ACTIVITY","reaction":{"name":"L-seryl-[myosin light chain] + ATP = O-phospho-L-seryl-[myosin light chain] + ADP + H(+)","reactionCrossReferences":[{"database":"Rhea","id":"RHEA:22004"},{"database":"Rhea","id":"RHEA-COMP:13684"},{"database":"Rhea","id":"RHEA-COMP:13685"},{"database":"ChEBI","id":"CHEBI:15378"},{"database":"ChEBI","id":"CHEBI:29999"},{"database":"ChEBI","id":"CHEBI:30616"},{"database":"ChEBI","id":"CHEBI:83421"},{"database":"ChEBI","id":"CHEBI:456216"}],"ecNumber":"2.7.11.18","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11113114"}]},"physiologicalReactions":[{"directionType":"left-to-right","reactionCrossReference":{"database":"Rhea","id":"RHEA:22005"},"evidences":[{"evidenceCode":"ECO:0000305","source":"PubMed","id":"11113114"}]}]},{"commentType":"CATALYTIC ACTIVITY","reaction":{"name":"L-threonyl-[myosin light chain] + ATP = O-phospho-L-threonyl-[myosin light chain] + ADP + H(+)","reactionCrossReferences":[{"database":"Rhea","id":"RHEA:53900"},{"database":"Rhea","id":"RHEA-COMP:13686"},{"database":"Rhea","id":"RHEA-COMP:13687"},{"database":"ChEBI","id":"CHEBI:15378"},{"database":"ChEBI","id":"CHEBI:30013"},{"database":"ChEBI","id":"CHEBI:30616"},{"database":"ChEBI","id":"CHEBI:61977"},{"database":"ChEBI","id":"CHEBI:456216"}],"ecNumber":"2.7.11.18","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11113114"}]},"physiologicalReactions":[{"directionType":"left-to-right","reactionCrossReference":{"database":"Rhea","id":"RHEA:53901"},"evidences":[{"evidenceCode":"ECO:0000305","source":"PubMed","id":"11113114"}]}]},{"commentType":"COFACTOR","cofactors":[{"name":"Mg(2+)","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11113114"}],"cofactorCrossReference":{"database":"ChEBI","id":"CHEBI:18420"}}]},{"commentType":"COFACTOR","cofactors":[{"name":"Ca(2+)","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11113114"}],"cofactorCrossReference":{"database":"ChEBI","id":"CHEBI:29108"}}]},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11113114"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11976941"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"14741352"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16284075"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16723733"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"21918590"}],"value":"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"}],"commentType":"ACTIVITY REGULATION"},{"commentType":"BIOPHYSICOCHEMICAL PROPERTIES","kineticParameters":{"maximumVelocities":[{"velocity":11.9,"unit":"umol/min/mg","enzyme":"enzyme (isoform 1 at 22 degrees Celsius)","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11113114"}]},{"velocity":10.9,"unit":"umol/min/mg","enzyme":"enzyme (isoform 1 at 22 degrees Celsius)","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11113114"}]}],"michaelisConstants":[{"constant":6.5,"unit":"uM","substrate":"MLC (isoform 1 at 22 degrees Celsius)","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11113114"}]},{"constant":7.2,"unit":"uM","substrate":"MLC (isoform 2 at 22 degrees Celsius)","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11113114"}]},{"constant":9.3,"unit":"uM","substrate":"MLC","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"29544503"}]}]}},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12408982"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18462678"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18587400"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19826488"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20053363"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20861316"}],"value":"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"}],"commentType":"SUBUNIT"},{"commentType":"INTERACTION","interactions":[{"interactantOne":{"uniProtKBAccession":"Q15746","intActId":"EBI-968482"},"interactantTwo":{"uniProtKBAccession":"Q9HD26","geneName":"GOPC","intActId":"EBI-349832"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q15746","intActId":"EBI-968482"},"interactantTwo":{"uniProtKBAccession":"P16333","geneName":"NCK1","intActId":"EBI-389883"},"numberOfExperiments":2,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q15746-1","intActId":"EBI-55022150"},"interactantTwo":{"uniProtKBAccession":"Q14318-2","geneName":"FKBP8","intActId":"EBI-10968017"},"numberOfExperiments":5,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q15746-7","intActId":"EBI-12189939"},"interactantTwo":{"uniProtKBAccession":"Q92624","geneName":"APPBP2","intActId":"EBI-743771"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q15746-7","intActId":"EBI-12189939"},"interactantTwo":{"uniProtKBAccession":"Q9HD26-2","geneName":"GOPC","intActId":"EBI-11102276"},"numberOfExperiments":5,"organismDiffer":false}]},{"commentType":"SUBCELLULAR LOCATION","note":{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15020676"}],"value":"Localized to stress fibers during interphase and to the cleavage furrow during mitosis"}]},"subcellularLocations":[{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20053363"}],"value":"Cytoplasm","id":"SL-0086"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20053363"}],"value":"Cell projection, lamellipodium","id":"SL-0291"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15020676"}],"value":"Cleavage furrow","id":"SL-0467"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15020676"}],"value":"Cytoplasm, cytoskeleton, stress fiber","id":"SL-0501"}}]},{"commentType":"ALTERNATIVE PRODUCTS","events":["Alternative promoter usage","Alternative splicing"],"isoforms":[{"name":{"value":"1"},"synonyms":[{"value":"Non-muscle isozyme"}],"isoformIds":["Q15746-1"],"isoformSequenceStatus":"Displayed"},{"name":{"value":"2"},"isoformIds":["Q15746-2"],"sequenceIds":["VSP_004791"],"isoformSequenceStatus":"Described"},{"name":{"value":"3A"},"isoformIds":["Q15746-3"],"sequenceIds":["VSP_004794"],"isoformSequenceStatus":"Described"},{"name":{"value":"3B"},"isoformIds":["Q15746-4"],"sequenceIds":["VSP_004791","VSP_004794"],"isoformSequenceStatus":"Described"},{"name":{"value":"4"},"isoformIds":["Q15746-5"],"sequenceIds":["VSP_004793"],"isoformSequenceStatus":"Described"},{"name":{"value":"Del-1790"},"isoformIds":["Q15746-6"],"sequenceIds":["VSP_004795"],"isoformSequenceStatus":"Described"},{"name":{"value":"5"},"synonyms":[{"value":"Smooth-muscle isozyme"}],"isoformIds":["Q15746-7"],"sequenceIds":["VSP_018845"],"isoformSequenceStatus":"Described"},{"name":{"value":"6"},"synonyms":[{"value":"Telokin"}],"isoformIds":["Q15746-8"],"sequenceIds":["VSP_018846"],"isoformSequenceStatus":"Described"},{"name":{"value":"7"},"isoformIds":["Q15746-9"],"sequenceIds":["VSP_053791"],"isoformSequenceStatus":"Described"},{"name":{"value":"8"},"isoformIds":["Q15746-10"],"sequenceIds":["VSP_018846","VSP_004795"],"isoformSequenceStatus":"Described"},{"name":{"value":"9"},"isoformIds":["Q15746-11"],"sequenceIds":["VSP_018845","VSP_004795"],"isoformSequenceStatus":"Described"}]},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10536370"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16835238"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20053363"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"8575746"}],"value":"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)"}],"commentType":"TISSUE SPECIFICITY"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16835238"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19011151"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19429448"}],"value":"Accumulates in individuals with asthma (at protein levels). Induced by tumor necrosis factor (TNF). Repressed by androgens (e.g. R1881)"}],"commentType":"INDUCTION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11113114"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12408982"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20861316"}],"value":"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"}],"commentType":"PTM"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q6PDN3"}],"value":"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)"}],"commentType":"PTM"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19826488"}],"value":"Acetylated at Lys-608 by NAA10/ARD1 via a calcium-dependent signaling; this acetylation represses kinase activity and reduces tumor cell migration"}],"commentType":"PTM"},{"commentType":"DISEASE","disease":{"diseaseId":"Aortic aneurysm, familial thoracic 7","diseaseAccession":"DI-03062","acronym":"AAT7","description":"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.","diseaseCrossReference":{"database":"MIM","id":"613780"},"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"21055718"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"28401540"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"29544503"}]},"note":{"texts":[{"value":"The disease is caused by variants affecting the gene represented in this entry"}]}},{"commentType":"DISEASE","disease":{"diseaseId":"Megacystis-microcolon-intestinal hypoperistalsis syndrome","diseaseAccession":"DI-05709","acronym":"MMIHS","description":"A form of megacystis-microcolon-intestinal hypoperistalsis syndrome, a congenital visceral myopathy primarily affecting females, and characterized by loss of smooth muscle contraction in the bladder and intestine. Affected individuals present at birth with functional obstruction of intestine, microcolon, dilation of bladder, and secondary hydronephrosis. The majority of cases have a fatal outcome due to malnutrition and sepsis, followed by multiorgan failure. MMIHS inheritance is autosomal recessive.","diseaseCrossReference":{"database":"MIM","id":"249210"},"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"28602422"}]},"note":{"texts":[{"value":"The disease is caused by variants affecting the gene represented in this entry"}]}},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000305","source":"PubMed","id":"19011151"}],"value":"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"}],"commentType":"MISCELLANEOUS"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"22015949"}],"value":"Transcribed from an alternative promoter resulting in the usage of Met-923 as initiator codon"}],"commentType":"MISCELLANEOUS","molecule":"Isoform 5"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"Transcribed from an alternative promoter resulting in the usage of Met-1761 as initiator codon. Has no catalytic activity. Initiator Met is removed"}],"commentType":"MISCELLANEOUS","molecule":"Isoform 6"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"Transcribed from an alternative promoter resulting in the usage of Met-1761 as initiator codon. Initiator Met is removed"}],"commentType":"MISCELLANEOUS","molecule":"Isoform 8"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"22015949"}],"value":"Transcribed from an alternative promoter resulting in the usage of Met-923 as initiator codon"}],"commentType":"MISCELLANEOUS","molecule":"Isoform 9"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family"}],"commentType":"SIMILARITY"},{"commentType":"SEQUENCE CAUTION","sequenceCautionType":"Frameshift","sequence":"AAD15922.1","evidences":[{"evidenceCode":"ECO:0000305"}]},{"commentType":"SEQUENCE CAUTION","sequenceCautionType":"Frameshift","sequence":"AAD15923.1","evidences":[{"evidenceCode":"ECO:0000305"}]},{"commentType":"SEQUENCE CAUTION","sequenceCautionType":"Frameshift","sequence":"AAD15924.1","evidences":[{"evidenceCode":"ECO:0000305"}]},{"commentType":"WEB RESOURCE","resourceName":"Wikipedia","resourceUrl":"https://en.wikipedia.org/wiki/Myosin_light-chain_kinase","ftp":false,"note":"Myosin light-chain kinase entry"},{"commentType":"WEB RESOURCE","resourceName":"Atlas of Genetics and Cytogenetics in Oncology and Haematology","resourceUrl":"https://atlasgeneticsoncology.org/gene/43364/MYLK","ftp":false}],"features":[{"type":"Chain","location":{"start":{"value":1,"modifier":"EXACT"},"end":{"value":1914,"modifier":"EXACT"}},"description":"Myosin 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