Myosin light chain kinase, smooth muscle

Details

Name
Myosin light chain kinase, smooth muscle
Synonyms
  • 2.7.11.18
  • Kinase-related protein
  • KRP
  • MLCK
  • MLCK1
  • MYLK1
  • Telokin
Gene Name
MYLK
Organism
Humans
Amino acid sequence
>lcl|BSEQ0051862|Myosin light chain kinase, smooth muscle
MGDVKLVASSHISKTSLSVDPSRVDSMPLTEAPAFILPPRNLCIKEGATAKFEGRVRGYP
EPQVTWHRNGQPITSGGRFLLDCGIRGTFSLVIHAVHEEDRGKYTCEATNGSGARQVTVE
LTVEGSFAKQLGQPVVSKTLGDRFSAPAVETRPSIWGECPPKFATKLGRVVVKEGQMGRF
SCKITGRPQPQVTWLKGNVPLQPSARVSVSEKNGMQVLEIHGVNQDDVGVYTCLVVNGSG
KASMSAELSIQGLDSANRSFVRETKATNSDVRKEVTNVISKESKLDSLEAAAKSKNCSSP
QRGGSPPWAANSQPQPPRESKLESCKDSPRTAPQTPVLQKTSSSITLQAARVQPEPRAPG
LGVLSPSGEERKRPAPPRPATFPTRQPGLGSQDVVSKAANRRIPMEGQRDSAFPKFESKP
QSQEVKENQTVKFRCEVSGIPKPEVAWFLEGTPVRRQEGSIEVYEDAGSHYLCLLKARTR
DSGTYSCTASNAQGQLSCSWTLQVERLAVMEVAPSFSSVLKDCAVIEGQDFVLQCSVRGT
PVPRITWLLNGQPIQYARSTCEAGVAELHIQDALPEDHGTYTCLAENALGQVSCSAWVTV
HEKKSSRKSEYLLPVAPSKPTAPIFLQGLSDLKVMDGSQVTMTVQVSGNPPPEVIWLHNG
NEIQESEDFHFEQRGTQHSLCIQEVFPEDTGTYTCEAWNSAGEVRTQAVLTVQEPHDGTQ
PWFISKPRSVTASLGQSVLISCAIAGDPFPTVHWLRDGKALCKDTGHFEVLQNEDVFTLV
LKKVQPWHAGQYEILLKNRVGECSCQVSLMLQNSSARALPRGREPASCEDLCGGGVGADG
GGSDRYGSLRPGWPARGQGWLEEEDGEDVRGVLKRRVETRQHTEEAIRQQEVEQLDFRDL
LGKKVSTKTLSEDDLKEIPAEQMDFRANLQRQVKPKTVSEEERKVHSPQQVDFRSVLAKK
GTSKTPVPEKVPPPKPATPDFRSVLGGKKKLPAENGSSSAETLNAKAVESSKPLSNAQPS
GPLKPVGNAKPAETLKPMGNAKPAETLKPMGNAKPDENLKSASKEELKKDVKNDVNCKRG
HAGTTDNEKRSESQGTAPAFKQKLQDVHVAEGKKLLLQCQVSSDPPATIIWTLNGKTLKT
TKFIILSQEGSLCSVSIEKALPEDRGLYKCVAKNDAGQAECSCQVTVDDAPASENTKAPE
MKSRRPKSSLPPVLGTESDATVKKKPAPKTPPKAAMPPQIIQFPEDQKVRAGESVELFGK
VTGTQPITCTWMKFRKQIQESEHMKVENSENGSKLTILAARQEHCGCYTLLVENKLGSRQ
AQVNLTVVDKPDPPAGTPCASDIRSSSLTLSWYGSSYDGGSAVQSYSIEIWDSANKTWKE
LATCRSTSFNVQDLLPDHEYKFRVRAINVYGTSEPSQESELTTVGEKPEEPKDEVEVSDD
DEKEPEVDYRTVTINTEQKVSDFYDIEERLGSGKFGQVFRLVEKKTRKVWAGKFFKAYSA
KEKENIRQEISIMNCLHHPKLVQCVDAFEEKANIVMVLEIVSGGELFERIIDEDFELTER
ECIKYMRQISEGVEYIHKQGIVHLDLKPENIMCVNKTGTRIKLIDFGLARRLENAGSLKV
LFGTPEFVAPEVINYEPIGYATDMWSIGVICYILVSGLSPFMGDNDNETLANVTSATWDF
DDEAFDEISDDAKDFISNLLKKDMKNRLDCTQCLQHPWLMKDTKNMEAKKLSKDRMKKYM
ARRKWQKTGNAVRAIGRLSSMAMISGLSGRKSSTGSPTSPLNAEKLESEEDVSQAFLEAV
AEEKPHVKPYFSKTIRDLEVVEGSAARFDCKIEGYPDPEVVWFKDDQSIRESRHFQIDYD
EDGNCSLIISDVCGDDDAKYTCKAVNSLGEATCTAELIVETMEEGEGEGEEEEE
Number of residues
1914
Molecular Weight
210713.455
Theoretical pI
Not Available
GO Classification
Functions
actin binding / ATP binding / calmodulin binding / metal ion binding / myosin light chain kinase activity
Processes
aorta smooth muscle tissue morphogenesis / bleb assembly / cellular hypotonic response / muscle contraction / positive regulation of calcium ion transport / positive regulation of cell migration / positive regulation of wound healing / protein phosphorylation / smooth muscle contraction / tonic smooth muscle contraction
Components
actin cytoskeleton / cleavage furrow / cytoplasm / cytosol / extracellular exosome / lamellipodium / plasma membrane / stress fiber
General 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.
Specific Function
Actin binding
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Cytoplasm
Gene sequence
>lcl|BSEQ0051863|Myosin light chain kinase, smooth muscle (MYLK)
ATGGGGGATGTGAAGCTGGTTGCCTCGTCACACATTTCCAAAACCTCCCTCAGTGTGGAT
CCCTCAAGAGTTGACTCCATGCCCCTGACAGAGGCCCCTGCTTTCATTTTGCCCCCTCGG
AACCTCTGCATCAAAGAAGGAGCCACCGCCAAGTTCGAAGGGCGGGTCCGGGGTTACCCA
GAGCCCCAGGTGACATGGCACAGAAACGGGCAACCCATCACCAGCGGGGGCCGCTTCCTG
CTGGATTGCGGCATCCGGGGGACTTTCAGCCTTGTGATTCATGCTGTCCATGAGGAGGAC
AGGGGAAAGTATACCTGTGAAGCCACCAATGGCAGTGGTGCTCGCCAGGTGACAGTGGAG
TTGACAGTAGAAGGAAGTTTTGCGAAGCAGCTTGGTCAGCCTGTTGTTTCCAAAACCTTA
GGGGATAGATTTTCAGCTCCAGCAGTGGAGACCCGTCCTAGCATCTGGGGGGAGTGCCCA
CCAAAGTTTGCTACCAAGCTGGGCCGAGTTGTGGTCAAAGAAGGACAGATGGGACGATTC
TCCTGCAAGATCACTGGCCGGCCCCAACCGCAGGTCACCTGGCTCAAGGGAAATGTTCCA
CTGCAGCCGAGTGCCCGTGTGTCTGTGTCTGAGAAGAACGGCATGCAGGTTCTGGAAATC
CATGGAGTCAACCAAGATGACGTGGGAGTGTACACGTGCCTGGTGGTGAACGGGTCGGGG
AAGGCCTCGATGTCAGCTGAACTTTCCATCCAAGGTTTGGACAGTGCCAATAGGTCATTT
GTGAGAGAAACAAAAGCCACCAATTCAGATGTCAGGAAAGAGGTGACCAATGTAATCTCA
AAGGAGTCGAAGCTGGACAGTCTGGAGGCTGCAGCCAAAAGCAAGAACTGCTCCAGCCCC
CAGAGAGGTGGCTCCCCACCCTGGGCTGCAAACAGCCAGCCTCAGCCCCCAAGGGAGTCC
AAGCTGGAGTCATGCAAGGACTCGCCCAGAACGGCCCCGCAGACCCCGGTCCTTCAGAAG
ACTTCCAGCTCCATCACCCTGCAGGCCGCAAGAGTTCAGCCGGAACCAAGAGCACCAGGC
CTGGGGGTCCTATCACCTTCTGGAGAAGAGAGGAAGAGGCCAGCTCCTCCCCGTCCAGCC
ACCTTCCCCACCAGGCAGCCTGGCCTGGGGAGCCAAGATGTTGTGAGCAAGGCTGCTAAC
AGGAGAATCCCCATGGAGGGCCAGAGGGATTCAGCATTCCCCAAATTTGAGAGCAAGCCC
CAAAGCCAGGAGGTCAAGGAAAATCAAACTGTCAAGTTCAGATGTGAAGTTTCCGGGATT
CCAAAGCCTGAAGTGGCCTGGTTCCTGGAAGGCACCCCCGTGAGGAGACAGGAAGGCAGC
ATTGAGGTTTATGAAGATGCTGGCTCCCATTACCTCTGCCTGCTGAAAGCCCGGACCAGG
GACAGTGGGACATACAGCTGCACTGCTTCCAACGCCCAAGGCCAGCTGTCCTGTAGCTGG
ACCCTCCAAGTGGAAAGGCTTGCCGTGATGGAGGTGGCCCCCTCCTTCTCCAGTGTCCTG
AAGGACTGCGCTGTTATTGAGGGCCAGGATTTTGTGCTGCAGTGCTCCGTACGGGGGACC
CCAGTGCCCCGGATCACTTGGCTGCTGAATGGGCAGCCCATCCAGTACGCTCGCTCCACC
TGCGAGGCCGGCGTGGCTGAGCTCCACATCCAGGATGCCCTGCCGGAGGACCATGGCACC
TACACCTGCCTAGCTGAGAATGCCTTGGGGCAGGTGTCCTGCAGCGCCTGGGTCACCGTC
CATGAAAAGAAGAGTAGCAGGAAGAGTGAGTACCTTCTGCCTGTGGCTCCCAGCAAGCCC
ACTGCACCCATCTTCCTGCAGGGCCTCTCTGATCTCAAAGTCATGGATGGAAGCCAGGTC
ACTATGACTGTCCAAGTGTCAGGGAATCCACCCCCTGAAGTCATCTGGCTGCACAATGGG
AATGAGATCCAAGAGTCAGAGGACTTCCACTTTGAACAGAGAGGAACTCAGCACAGCCTT
TGTATCCAGGAAGTGTTCCCGGAGGACACGGGCACGTACACCTGCGAGGCCTGGAACAGC
GCTGGAGAGGTCCGCACCCAGGCCGTGCTCACGGTACAAGAGCCTCACGATGGCACCCAG
CCCTGGTTCATCAGTAAGCCTCGCTCAGTGACAGCCTCCCTGGGCCAGAGTGTCCTCATC
TCCTGCGCCATAGCTGGTGACCCCTTTCCTACCGTGCACTGGCTCAGAGATGGCAAAGCC
CTCTGCAAAGACACTGGCCACTTCGAGGTGCTTCAGAATGAGGACGTGTTCACCCTGGTT
CTAAAGAAGGTGCAGCCCTGGCATGCCGGCCAGTATGAGATCCTGCTCAAGAACCGGGTT
GGCGAATGCAGTTGCCAGGTGTCACTGATGCTACAGAACAGCTCTGCCAGAGCCCTTCCA
CGGGGGAGGGAGCCTGCCAGCTGCGAGGACCTCTGTGGTGGAGGAGTTGGTGCTGATGGT
GGTGGTAGTGACCGCTATGGGTCCCTGAGGCCTGGCTGGCCAGCAAGAGGGCAGGGTTGG
CTAGAGGAGGAAGACGGCGAGGACGTGCGAGGGGTGCTGAAGAGGCGCGTGGAGACGAGG
CAGCACACTGAGGAGGCGATCCGCCAGCAGGAGGTGGAGCAGCTGGACTTCCGAGACCTC
CTGGGGAAGAAGGTGAGTACAAAGACCCTATCGGAAGACGACCTGAAGGAGATCCCAGCC
GAGCAGATGGATTTCCGTGCCAACCTGCAGCGGCAAGTGAAGCCAAAGACTGTGTCTGAG
GAAGAGAGGAAGGTGCACAGCCCCCAGCAGGTCGATTTTCGCTCTGTCCTGGCCAAGAAG
GGGACTTCCAAGACCCCCGTGCCTGAGAAGGTGCCACCGCCAAAACCTGCCACCCCGGAT
TTTCGCTCAGTGCTGGGTGGCAAGAAGAAATTACCAGCAGAGAATGGCAGCAGCAGTGCC
GAGACCCTGAATGCCAAGGCAGTGGAGAGTTCCAAGCCCCTGAGCAATGCACAGCCTTCA
GGGCCCTTGAAACCCGTGGGCAACGCCAAGCCTGCTGAGACCCTGAAGCCAATGGGCAAC
GCCAAGCCTGCCGAGACCCTGAAGCCCATGGGCAATGCCAAGCCTGATGAGAACCTGAAA
TCCGCTAGCAAAGAAGAACTCAAGAAAGACGTTAAGAATGATGTGAACTGCAAGAGAGGC
CATGCAGGGACCACAGATAATGAAAAGAGATCAGAGAGCCAGGGGACAGCCCCAGCCTTC
AAGCAGAAGCTGCAAGATGTTCATGTGGCAGAGGGCAAGAAGCTGCTGCTCCAGTGCCAG
GTGTCTTCTGACCCCCCAGCCACCATCATCTGGACGCTGAACGGAAAGACCCTCAAGACC
ACCAAGTTCATCATCCTCTCCCAGGAAGGCTCACTCTGCTCCGTCTCCATCGAGAAGGCA
CTGCCTGAGGACAGAGGCTTATACAAGTGTGTAGCCAAGAATGACGCTGGCCAGGCGGAG
TGCTCCTGCCAAGTCACCGTGGATGATGCTCCAGCCAGTGAGAACACCAAGGCCCCAGAG
ATGAAATCCCGGAGGCCCAAGAGCTCTCTTCCTCCCGTGCTAGGAACTGAGAGTGATGCG
ACTGTGAAAAAGAAACCTGCCCCCAAGACACCTCCGAAGGCAGCAATGCCCCCTCAGATC
ATCCAGTTCCCTGAGGACCAGAAGGTACGCGCAGGAGAGTCAGTGGAGCTGTTTGGCAAA
GTGACAGGCACTCAGCCCATCACCTGTACCTGGATGAAGTTCCGAAAGCAGATCCAGGAA
AGCGAGCACATGAAGGTGGAGAACAGCGAGAATGGCAGCAAGCTCACCATCCTGGCCGCG
CGCCAGGAGCACTGCGGCTGCTACACACTGCTGGTGGAGAACAAGCTGGGCAGCAGGCAG
GCCCAGGTCAACCTCACTGTCGTGGATAAGCCAGACCCCCCAGCTGGCACACCTTGTGCC
TCTGACATTCGGAGCTCCTCACTGACCCTGTCCTGGTATGGCTCCTCATATGATGGGGGC
AGTGCTGTACAGTCCTACAGCATCGAGATCTGGGACTCAGCCAACAAGACGTGGAAGGAA
CTAGCCACATGCCGCAGCACCTCTTTCAACGTCCAGGACCTGCTGCCTGACCACGAATAT
AAGTTCCGTGTACGTGCAATCAACGTGTATGGAACCAGTGAGCCAAGCCAGGAGTCTGAA
CTCACAACGGTAGGAGAGAAACCTGAAGAGCCGAAGGATGAAGTGGAGGTGTCAGATGAT
GATGAGAAGGAGCCCGAGGTTGATTACCGGACAGTGACAATCAATACTGAACAAAAAGTA
TCTGACTTCTACGACATTGAGGAGAGATTAGGATCTGGGAAATTTGGACAGGTCTTTCGA
CTTGTAGAAAAGAAAACTCGAAAAGTCTGGGCAGGGAAGTTCTTCAAGGCATATTCAGCA
AAAGAGAAAGAGAATATCCGGCAGGAGATTAGCATCATGAACTGCCTCCACCACCCTAAG
CTGGTCCAGTGTGTGGATGCCTTTGAAGAAAAGGCCAACATCGTCATGGTCCTGGAGATC
GTGTCAGGAGGGGAGCTGTTTGAGCGCATCATTGACGAGGACTTTGAGCTGACGGAGCGT
GAGTGCATCAAGTACATGCGGCAGATCTCGGAGGGAGTGGAGTACATCCACAAGCAGGGC
ATCGTGCACCTGGACCTCAAGCCGGAGAACATCATGTGTGTCAACAAGACGGGCACCAGG
ATCAAGCTCATCGACTTTGGTCTGGCCAGGAGGCTGGAGAATGCGGGGTCTCTGAAGGTC
CTCTTTGGCACCCCAGAATTTGTGGCTCCTGAAGTGATCAACTATGAGCCCATCGGCTAC
GCCACAGACATGTGGAGCATCGGGGTCATCTGCTACATCCTAGTCAGTGGCCTTTCCCCC
TTCATGGGAGACAACGATAACGAAACCTTGGCCAACGTTACCTCAGCCACCTGGGACTTC
GACGACGAGGCATTCGATGAGATCTCCGACGATGCCAAGGATTTCATCAGCAATCTGCTG
AAGAAAGATATGAAAAACCGCCTGGACTGCACGCAGTGCCTTCAGCATCCATGGCTAATG
AAAGATACCAAGAACATGGAGGCCAAGAAACTCTCCAAGGACCGGATGAAGAAGTACATG
GCAAGAAGGAAATGGCAGAAAACGGGCAATGCTGTGAGAGCCATTGGAAGACTGTCCTCT
ATGGCAATGATCTCAGGGCTCAGTGGCAGGAAATCCTCAACAGGGTCACCAACCAGCCCG
CTCAATGCAGAAAAACTAGAATCTGAAGAAGATGTGTCCCAAGCTTTCCTTGAGGCTGTT
GCTGAGGAAAAGCCTCATGTAAAACCCTATTTCTCTAAGACCATTCGCGATTTAGAAGTT
GTGGAGGGAAGTGCTGCTAGATTTGACTGCAAGATTGAAGGATACCCAGACCCCGAGGTT
GTCTGGTTCAAAGATGACCAGTCAATCAGGGAGTCCCGCCACTTCCAGATAGACTACGAT
GAGGACGGGAACTGCTCTTTAATTATTAGTGATGTTTGCGGGGATGACGATGCCAAGTAC
ACCTGCAAGGCTGTCAACAGTCTTGGAGAAGCCACCTGCACAGCAGAGCTCATTGTGGAA
ACGATGGAGGAAGGTGAAGGGGAAGGGGAAGAGGAAGAAGAGTGA
Chromosome Location
3
Locus
3q21.1
External Identifiers
ResourceLink
UniProtKB IDQ15746
UniProtKB Entry NameMYLK_HUMAN
HGNC IDHGNC:7590
General References
  1. Potier MC, Chelot E, Pekarsky Y, Gardiner K, Rossier J, Turnell WG: The human myosin light chain kinase (MLCK) from hippocampus: cloning, sequencing, expression, and localization to 3qcen-q21. Genomics. 1995 Oct 10;29(3):562-70. [Article]
  2. Garcia JG, Lazar V, Gilbert-McClain LI, Gallagher PJ, Verin AD: Myosin light chain kinase in endothelium: molecular cloning and regulation. Am J Respir Cell Mol Biol. 1997 May;16(5):489-94. [Article]
  3. Lazar V, Garcia JG: A single human myosin light chain kinase gene (MLCK; MYLK). Genomics. 1999 Apr 15;57(2):256-67. [Article]
  4. Birukov KG, Csortos C, Marzilli L, Dudek S, Ma SF, Bresnick AR, Verin AD, Cotter RJ, Garcia JG: Differential regulation of alternatively spliced endothelial cell myosin light chain kinase isoforms by p60(Src). J Biol Chem. 2001 Mar 16;276(11):8567-73. Epub 2000 Dec 11. [Article]
  5. Watterson DM, Schavocky JP, Guo L, Weiss C, Chlenski A, Shirinsky VP, Van Eldik LJ, Haiech J: Analysis of the kinase-related protein gene found at human chromosome 3q21 in a multi-gene cluster: organization, expression, alternative splicing, and polymorphic marker. J Cell Biochem. 1999 Dec 1;75(3):481-91. [Article]
  6. Clayburgh DR, Rosen S, Witkowski ED, Wang F, Blair S, Dudek S, Garcia JG, Alverdy JC, Turner JR: A differentiation-dependent splice variant of myosin light chain kinase, MLCK1, regulates epithelial tight junction permeability. J Biol Chem. 2004 Dec 31;279(53):55506-13. Epub 2004 Oct 26. [Article]
  7. Dulyaninova NG, Patskovsky YV, Bresnick AR: The N-terminus of the long MLCK induces a disruption in normal spindle morphology and metaphase arrest. J Cell Sci. 2004 Mar 15;117(Pt 8):1481-93. [Article]
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  18. Zhou X, Liu Y, You J, Zhang H, Zhang X, Ye L: Myosin light-chain kinase contributes to the proliferation and migration of breast cancer cells through cross-talk with activated ERK1/2. Cancer Lett. 2008 Nov 8;270(2):312-27. doi: 10.1016/j.canlet.2008.05.028. Epub 2008 Aug 16. [Article]
  19. Zahedi RP, Lewandrowski U, Wiesner J, Wortelkamp S, Moebius J, Schutz C, Walter U, Gambaryan S, Sickmann A: Phosphoproteome of resting human platelets. J Proteome Res. 2008 Feb;7(2):526-34. Epub 2007 Dec 19. [Article]
  20. Xu J, Gao XP, Ramchandran R, Zhao YY, Vogel SM, Malik AB: Nonmuscle myosin light-chain kinase mediates neutrophil transmigration in sepsis-induced lung inflammation by activating beta2 integrins. Nat Immunol. 2008 Aug;9(8):880-6. doi: 10.1038/ni.1628. Epub 2008 Jun 29. [Article]
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Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB12010Fostamatinibapproved, investigationalunknowninhibitorDetails