P29294 · MYLK_RABIT

Function

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 Ca2+ entry and subsequent activation of volume-sensitive organic osmolyte/anion channels (VSOAC) in cervical cancer cells (By similarity).

Catalytic activity

Cofactor

Protein has several cofactor binding sites:
Mg2+ (UniProtKB | Rhea| CHEBI:18420 )
Ca2+ (UniProtKB | Rhea| CHEBI:29108 )

Activity regulation

All catalytically active isoforms require binding to calcium and calmodulin for activation.

Kinetics

KM SUBSTRATE pH TEMPERATURE[C] NOTES EVIDENCE
5.2 μMMLC22isoform Smooth-muscle
Vmax pH TEMPERATURE[C] NOTES EVIDENCE
17 μmol/min/mg22isoform Smooth-muscle

Features

Showing features for binding site, active site.

TypeIDPosition(s)Description
Binding site702-710ATP (UniProtKB | ChEBI)
Binding site725ATP (UniProtKB | ChEBI)
Active site817Proton acceptor

GO annotations

AspectTerm
Cellular Componentcleavage furrow
Cellular Componentcytoplasm
Cellular Componentlamellipodium
Cellular Componentstress fiber
Molecular Functionactin binding
Molecular FunctionATP binding
Molecular Functioncalmodulin binding
Molecular Functionmetal ion binding
Molecular Functionmyosin light chain kinase activity

Keywords

Enzyme and pathway databases

Names & Taxonomy

Protein names

Gene names

    • Name
      MYLK

Organism names

  • Taxonomic identifier
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Lagomorpha > Leporidae > Oryctolagus

Accessions

  • Primary accession
    P29294
  • Secondary accessions
    • Q28729

Proteomes

Subcellular Location

Cytoplasm
Cleavage furrow
Note: Localized to stress fibers during interphase and to the cleavage furrow during mitosis.

Keywords

PTM/Processing

Features

Showing features for chain, disulfide bond, modified residue.

TypeIDPosition(s)Description
ChainPRO_00004037331-1142Myosin light chain kinase, smooth muscle, deglutamylated form
ChainPRO_00000243571-1147Myosin light chain kinase, smooth muscle
Disulfide bond350↔401
Modified residue670Phosphoserine
Modified residue681Phosphotyrosine; by ABL1
Modified residue807Phosphotyrosine; by ABL1
Modified residue867Phosphotyrosine; by ABL1
Modified residue991Phosphoserine
Modified residue992Phosphoserine
Modified residue1004Phosphoserine
Modified residue1005Phosphoserine
Modified residue1008Phosphoserine
Modified residue1010Phosphothreonine
Modified residue1011Phosphoserine
Disulfide bond1062↔1114

Post-translational modification

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).
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 promotes CTTN binding (By similarity).

Keywords

Proteomic databases

PTM databases

Expression

Tissue specificity

Isoform Telokin is found in all smooth muscle tested except the aorta. It is not present in non-muscle tissue.

Interaction

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 (By similarity).

Protein-protein interaction databases

Structure

Family & Domains

Features

Showing features for region, compositional bias, repeat, domain.

TypeIDPosition(s)Description
Region1-41Actin-binding
Region1-330Disordered
Compositional bias13-27Basic and acidic residues
Region26-41Calmodulin-binding
Repeat100-1111
Region100-28816 X 12 AA tandem repeats
Repeat112-1232
Repeat124-1323; truncated
Repeat133-1444
Repeat145-1565
Repeat157-1686
Repeat169-1807
Repeat181-1928
Repeat193-2049
Repeat205-21610
Repeat217-22811
Repeat229-24012
Repeat241-25213
Repeat253-26414
Repeat265-27615
Repeat277-28816
Compositional bias290-317Basic and acidic residues
Region292-692Actin-binding (calcium/calmodulin-insensitive)
Domain329-417Ig-like C2-type 1
Region424-476Disordered
Domain469-557Ig-like C2-type 2
Domain565-657Fibronectin type-III
Region644-678Disordered
Domain696-951Protein kinase
Region943-1006Calmodulin-binding
Compositional bias999-1015Polar residues
Region999-1019Disordered
Domain1041-1130Ig-like C2-type 3

Sequence similarities

Keywords

Phylogenomic databases

Family and domain databases

Sequence & Isoform

Align isoforms (2)
  • Sequence status
    Complete

This entry describes 2 isoforms produced by Alternative promoter usage.

P29294-1

This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

  • Name
    1
  • Synonyms
    Smooth-muscle
  • See also
    sequence in UniParc or sequence clusters in UniRef
  • Length
    1,147
  • Mass (Da)
    125,720
  • Last updated
    1998-07-15 v2
  • Checksum
    F039E624C6E31024
MDFRANLQRQVKPKTVSEEERKVHSPQQVDFRSVLAKKGTPKTPVPEKAPPPKPATPDFRSVLGSKKKLPAENGSSNAEALNVKATESPKLVGNAPLSGSLKPVANAKPAETLKPVANTKPAETLKPVANAETLKPMGNAKPAESSKPVGNTKPAETLKPVGNTKPAETLKPVGNIKPAETLKPVGNIKPAETLKPVGNTKPTETLKPVANAKSAETLKPIANTKPAETLKPVGNAKPAETLKPVGNAKPAETLKPVGNAKPAETLKPVGNAKPAETLKAVANAKPAETPKPAGKEELKKEVQNDVNCKREKAGAADNEKPPASPGTAPTFKEKLQDVRVAEGEKLLLQCQVSSEPPATITWTLNGKTLKTTKFVILSQEGSLCSVSIEKALPEDRGLYKCVAKNAAPEAECSCHVTVHDAPASENAKAPEMKSRRPKSSLPPVLGTESDATVKKKPAPKTPPKAATPPQIPQFPEDQKVRAGERVELFGKVAGTQPITCTWMKFRKQIQDSEHIKVENSEAGSKLTILAARQEHCGCYTLLVENKLGSRQAQVNLTVVDKPDPPAGTPCASDIRSSSLTLSWYGSSYDGGSAVQSYSVEIWDSVDKMWTELATCRSTSFNVRDLLPDREYKFRVRAINVYGTSEPSQESELTTVGEKPEEPKDEVEEVSDDDEKEPEVDYRTVTVNTEQKVSDFYDIEERLGSGKFGQVFRLVEKKTGKIWAGKFFKAYSAKEKENIPAEIGIMNCLHHPKLVQCVDAFEEKANIVMVLEIVSGGELFERIIDEDFELTERECIKYMRQISEGVEYIHKQGIVHLDLKPENIMCVNKTGTRIKLIDFGLARRLENAGSLKVLFGTPEFVAPEVINYEPISYATDMWSIGVICYILVSGLSPFMGDNDNETLANVTSATWDFDDEAFDEISDDAKDFISNLLKKDMKNRLDCTQCLQHPWLMKDTKNMEAKKLSKDRMKKYMARRKWQKTGNAVRAIGRLSSMAMISGLSGRKSSTGSPTSPLTAERLETEEDVSQAFLEAVAEEKPHVKPYFSKTIRDLEVVEGSAARFDCKIEGYPDPEVVWFKDDQSIRESRHFQIDYDEDGNCSLIISDVCGDDDAKYTCKAVNSLGEATCTAELIVETMEEGEGEGEEEEEE

P29294-3

  • Name
    3
  • Synonyms
    Telokin
  • Note
    Has no catalytic activity.
  • See also
    sequence in UniParc or sequence clusters in UniRef
  • Differences from canonical

Features

Showing features for alternative sequence, compositional bias, sequence conflict.

TypeIDPosition(s)Description
Alternative sequenceVSP_0188491-992in isoform 3
Compositional bias13-27Basic and acidic residues
Compositional bias290-317Basic and acidic residues
Compositional bias999-1015Polar residues
Sequence conflict1114in Ref. 3; AAA31409

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
M76233
EMBL· GenBank· DDBJ
AAA73093.1
EMBL· GenBank· DDBJ
mRNA
M76234
EMBL· GenBank· DDBJ
AAA31408.1
EMBL· GenBank· DDBJ
Genomic DNA
M76181
EMBL· GenBank· DDBJ
AAA31409.1
EMBL· GenBank· DDBJ
mRNA

Similar Proteins

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