P29294 · MYLK_RABIT
- ProteinMyosin light chain kinase, smooth muscle
- GeneMYLK
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids1147 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
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
- ATP + L-seryl-[myosin light chain] = ADP + H+ + O-phospho-L-seryl-[myosin light chain]
Cofactor
Protein has several cofactor binding sites:
Activity regulation
All catalytically active isoforms require binding to calcium and calmodulin for activation.
Kinetics
KM | SUBSTRATE | pH | TEMPERATURE[C] | NOTES | EVIDENCE | |
---|---|---|---|---|---|---|
5.2 μM | MLC | 22 | isoform Smooth-muscle |
Vmax | pH | TEMPERATURE[C] | NOTES | EVIDENCE | |
---|---|---|---|---|---|
17 μmol/min/mg | 22 | isoform Smooth-muscle |
Features
Showing features for binding site, active site.
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | cleavage furrow | |
Cellular Component | cytoplasm | |
Cellular Component | lamellipodium | |
Cellular Component | stress fiber | |
Molecular Function | actin binding | |
Molecular Function | ATP binding | |
Molecular Function | calmodulin binding | |
Molecular Function | metal ion binding | |
Molecular Function | myosin light chain kinase activity |
Keywords
- Molecular function
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameMyosin light chain kinase, smooth muscle
- EC number
- Short namesMLCK; smMLCK
- Alternative names
- Cleaved into 1 chains
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Lagomorpha > Leporidae > Oryctolagus
Accessions
- Primary accessionP29294
- Secondary accessions
Proteomes
Subcellular Location
UniProt Annotation
GO Annotation
Note: Localized to stress fibers during interphase and to the cleavage furrow during mitosis.
Keywords
- Cellular component
PTM/Processing
Features
Showing features for chain, disulfide bond, modified residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000403733 | 1-1142 | Myosin light chain kinase, smooth muscle, deglutamylated form | |||
Sequence: MDFRANLQRQVKPKTVSEEERKVHSPQQVDFRSVLAKKGTPKTPVPEKAPPPKPATPDFRSVLGSKKKLPAENGSSNAEALNVKATESPKLVGNAPLSGSLKPVANAKPAETLKPVANTKPAETLKPVANAETLKPMGNAKPAESSKPVGNTKPAETLKPVGNTKPAETLKPVGNIKPAETLKPVGNIKPAETLKPVGNTKPTETLKPVANAKSAETLKPIANTKPAETLKPVGNAKPAETLKPVGNAKPAETLKPVGNAKPAETLKPVGNAKPAETLKAVANAKPAETPKPAGKEELKKEVQNDVNCKREKAGAADNEKPPASPGTAPTFKEKLQDVRVAEGEKLLLQCQVSSEPPATITWTLNGKTLKTTKFVILSQEGSLCSVSIEKALPEDRGLYKCVAKNAAPEAECSCHVTVHDAPASENAKAPEMKSRRPKSSLPPVLGTESDATVKKKPAPKTPPKAATPPQIPQFPEDQKVRAGERVELFGKVAGTQPITCTWMKFRKQIQDSEHIKVENSEAGSKLTILAARQEHCGCYTLLVENKLGSRQAQVNLTVVDKPDPPAGTPCASDIRSSSLTLSWYGSSYDGGSAVQSYSVEIWDSVDKMWTELATCRSTSFNVRDLLPDREYKFRVRAINVYGTSEPSQESELTTVGEKPEEPKDEVEEVSDDDEKEPEVDYRTVTVNTEQKVSDFYDIEERLGSGKFGQVFRLVEKKTGKIWAGKFFKAYSAKEKENIPAEIGIMNCLHHPKLVQCVDAFEEKANIVMVLEIVSGGELFERIIDEDFELTERECIKYMRQISEGVEYIHKQGIVHLDLKPENIMCVNKTGTRIKLIDFGLARRLENAGSLKVLFGTPEFVAPEVINYEPISYATDMWSIGVICYILVSGLSPFMGDNDNETLANVTSATWDFDDEAFDEISDDAKDFISNLLKKDMKNRLDCTQCLQHPWLMKDTKNMEAKKLSKDRMKKYMARRKWQKTGNAVRAIGRLSSMAMISGLSGRKSSTGSPTSPLTAERLETEEDVSQAFLEAVAEEKPHVKPYFSKTIRDLEVVEGSAARFDCKIEGYPDPEVVWFKDDQSIRESRHFQIDYDEDGNCSLIISDVCGDDDAKYTCKAVNSLGEATCTAELIVETMEEGEGEGE | ||||||
Chain | PRO_0000024357 | 1-1147 | Myosin light chain kinase, smooth muscle | |||
Sequence: MDFRANLQRQVKPKTVSEEERKVHSPQQVDFRSVLAKKGTPKTPVPEKAPPPKPATPDFRSVLGSKKKLPAENGSSNAEALNVKATESPKLVGNAPLSGSLKPVANAKPAETLKPVANTKPAETLKPVANAETLKPMGNAKPAESSKPVGNTKPAETLKPVGNTKPAETLKPVGNIKPAETLKPVGNIKPAETLKPVGNTKPTETLKPVANAKSAETLKPIANTKPAETLKPVGNAKPAETLKPVGNAKPAETLKPVGNAKPAETLKPVGNAKPAETLKAVANAKPAETPKPAGKEELKKEVQNDVNCKREKAGAADNEKPPASPGTAPTFKEKLQDVRVAEGEKLLLQCQVSSEPPATITWTLNGKTLKTTKFVILSQEGSLCSVSIEKALPEDRGLYKCVAKNAAPEAECSCHVTVHDAPASENAKAPEMKSRRPKSSLPPVLGTESDATVKKKPAPKTPPKAATPPQIPQFPEDQKVRAGERVELFGKVAGTQPITCTWMKFRKQIQDSEHIKVENSEAGSKLTILAARQEHCGCYTLLVENKLGSRQAQVNLTVVDKPDPPAGTPCASDIRSSSLTLSWYGSSYDGGSAVQSYSVEIWDSVDKMWTELATCRSTSFNVRDLLPDREYKFRVRAINVYGTSEPSQESELTTVGEKPEEPKDEVEEVSDDDEKEPEVDYRTVTVNTEQKVSDFYDIEERLGSGKFGQVFRLVEKKTGKIWAGKFFKAYSAKEKENIPAEIGIMNCLHHPKLVQCVDAFEEKANIVMVLEIVSGGELFERIIDEDFELTERECIKYMRQISEGVEYIHKQGIVHLDLKPENIMCVNKTGTRIKLIDFGLARRLENAGSLKVLFGTPEFVAPEVINYEPISYATDMWSIGVICYILVSGLSPFMGDNDNETLANVTSATWDFDDEAFDEISDDAKDFISNLLKKDMKNRLDCTQCLQHPWLMKDTKNMEAKKLSKDRMKKYMARRKWQKTGNAVRAIGRLSSMAMISGLSGRKSSTGSPTSPLTAERLETEEDVSQAFLEAVAEEKPHVKPYFSKTIRDLEVVEGSAARFDCKIEGYPDPEVVWFKDDQSIRESRHFQIDYDEDGNCSLIISDVCGDDDAKYTCKAVNSLGEATCTAELIVETMEEGEGEGEEEEEE | ||||||
Disulfide bond | 350↔401 | |||||
Sequence: CQVSSEPPATITWTLNGKTLKTTKFVILSQEGSLCSVSIEKALPEDRGLYKC | ||||||
Modified residue | 670 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 681 | Phosphotyrosine; by ABL1 | ||||
Sequence: Y | ||||||
Modified residue | 807 | Phosphotyrosine; by ABL1 | ||||
Sequence: Y | ||||||
Modified residue | 867 | Phosphotyrosine; by ABL1 | ||||
Sequence: Y | ||||||
Modified residue | 991 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 992 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 1004 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 1005 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 1008 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 1010 | Phosphothreonine | ||||
Sequence: T | ||||||
Modified residue | 1011 | Phosphoserine | ||||
Sequence: S | ||||||
Disulfide bond | 1062↔1114 | |||||
Sequence: CKIEGYPDPEVVWFKDDQSIRESRHFQIDYDEDGNCSLIISDVCGDDDAKYTC |
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
- PTM
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).
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.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 1-41 | Actin-binding | ||||
Sequence: MDFRANLQRQVKPKTVSEEERKVHSPQQVDFRSVLAKKGTP | ||||||
Region | 1-330 | Disordered | ||||
Sequence: MDFRANLQRQVKPKTVSEEERKVHSPQQVDFRSVLAKKGTPKTPVPEKAPPPKPATPDFRSVLGSKKKLPAENGSSNAEALNVKATESPKLVGNAPLSGSLKPVANAKPAETLKPVANTKPAETLKPVANAETLKPMGNAKPAESSKPVGNTKPAETLKPVGNTKPAETLKPVGNIKPAETLKPVGNIKPAETLKPVGNTKPTETLKPVANAKSAETLKPIANTKPAETLKPVGNAKPAETLKPVGNAKPAETLKPVGNAKPAETLKPVGNAKPAETLKAVANAKPAETPKPAGKEELKKEVQNDVNCKREKAGAADNEKPPASPGTAPT | ||||||
Compositional bias | 13-27 | Basic and acidic residues | ||||
Sequence: PKTVSEEERKVHSPQ | ||||||
Region | 26-41 | Calmodulin-binding | ||||
Sequence: PQQVDFRSVLAKKGTP | ||||||
Repeat | 100-111 | 1 | ||||
Sequence: SLKPVANAKPAE | ||||||
Region | 100-288 | 16 X 12 AA tandem repeats | ||||
Sequence: SLKPVANAKPAETLKPVANTKPAETLKPVANAETLKPMGNAKPAESSKPVGNTKPAETLKPVGNTKPAETLKPVGNIKPAETLKPVGNIKPAETLKPVGNTKPTETLKPVANAKSAETLKPIANTKPAETLKPVGNAKPAETLKPVGNAKPAETLKPVGNAKPAETLKPVGNAKPAETLKAVANAKPAE | ||||||
Repeat | 112-123 | 2 | ||||
Sequence: TLKPVANTKPAE | ||||||
Repeat | 124-132 | 3; truncated | ||||
Sequence: TLKPVANAE | ||||||
Repeat | 133-144 | 4 | ||||
Sequence: TLKPMGNAKPAE | ||||||
Repeat | 145-156 | 5 | ||||
Sequence: SSKPVGNTKPAE | ||||||
Repeat | 157-168 | 6 | ||||
Sequence: TLKPVGNTKPAE | ||||||
Repeat | 169-180 | 7 | ||||
Sequence: TLKPVGNIKPAE | ||||||
Repeat | 181-192 | 8 | ||||
Sequence: TLKPVGNIKPAE | ||||||
Repeat | 193-204 | 9 | ||||
Sequence: TLKPVGNTKPTE | ||||||
Repeat | 205-216 | 10 | ||||
Sequence: TLKPVANAKSAE | ||||||
Repeat | 217-228 | 11 | ||||
Sequence: TLKPIANTKPAE | ||||||
Repeat | 229-240 | 12 | ||||
Sequence: TLKPVGNAKPAE | ||||||
Repeat | 241-252 | 13 | ||||
Sequence: TLKPVGNAKPAE | ||||||
Repeat | 253-264 | 14 | ||||
Sequence: TLKPVGNAKPAE | ||||||
Repeat | 265-276 | 15 | ||||
Sequence: TLKPVGNAKPAE | ||||||
Repeat | 277-288 | 16 | ||||
Sequence: TLKAVANAKPAE | ||||||
Compositional bias | 290-317 | Basic and acidic residues | ||||
Sequence: PKPAGKEELKKEVQNDVNCKREKAGAAD | ||||||
Region | 292-692 | Actin-binding (calcium/calmodulin-insensitive) | ||||
Sequence: PAGKEELKKEVQNDVNCKREKAGAADNEKPPASPGTAPTFKEKLQDVRVAEGEKLLLQCQVSSEPPATITWTLNGKTLKTTKFVILSQEGSLCSVSIEKALPEDRGLYKCVAKNAAPEAECSCHVTVHDAPASENAKAPEMKSRRPKSSLPPVLGTESDATVKKKPAPKTPPKAATPPQIPQFPEDQKVRAGERVELFGKVAGTQPITCTWMKFRKQIQDSEHIKVENSEAGSKLTILAARQEHCGCYTLLVENKLGSRQAQVNLTVVDKPDPPAGTPCASDIRSSSLTLSWYGSSYDGGSAVQSYSVEIWDSVDKMWTELATCRSTSFNVRDLLPDREYKFRVRAINVYGTSEPSQESELTTVGEKPEEPKDEVEEVSDDDEKEPEVDYRTVTVNTEQKV | ||||||
Domain | 329-417 | Ig-like C2-type 1 | ||||
Sequence: PTFKEKLQDVRVAEGEKLLLQCQVSSEPPATITWTLNGKTLKTTKFVILSQEGSLCSVSIEKALPEDRGLYKCVAKNAAPEAECSCHVT | ||||||
Region | 424-476 | Disordered | ||||
Sequence: SENAKAPEMKSRRPKSSLPPVLGTESDATVKKKPAPKTPPKAATPPQIPQFPE | ||||||
Domain | 469-557 | Ig-like C2-type 2 | ||||
Sequence: PQIPQFPEDQKVRAGERVELFGKVAGTQPITCTWMKFRKQIQDSEHIKVENSEAGSKLTILAARQEHCGCYTLLVENKLGSRQAQVNLT | ||||||
Domain | 565-657 | Fibronectin type-III | ||||
Sequence: PAGTPCASDIRSSSLTLSWYGSSYDGGSAVQSYSVEIWDSVDKMWTELATCRSTSFNVRDLLPDREYKFRVRAINVYGTSEPSQESELTTVGE | ||||||
Region | 644-678 | Disordered | ||||
Sequence: SEPSQESELTTVGEKPEEPKDEVEEVSDDDEKEPE | ||||||
Domain | 696-951 | Protein kinase | ||||
Sequence: YDIEERLGSGKFGQVFRLVEKKTGKIWAGKFFKAYSAKEKENIPAEIGIMNCLHHPKLVQCVDAFEEKANIVMVLEIVSGGELFERIIDEDFELTERECIKYMRQISEGVEYIHKQGIVHLDLKPENIMCVNKTGTRIKLIDFGLARRLENAGSLKVLFGTPEFVAPEVINYEPISYATDMWSIGVICYILVSGLSPFMGDNDNETLANVTSATWDFDDEAFDEISDDAKDFISNLLKKDMKNRLDCTQCLQHPWL | ||||||
Region | 943-1006 | Calmodulin-binding | ||||
Sequence: TQCLQHPWLMKDTKNMEAKKLSKDRMKKYMARRKWQKTGNAVRAIGRLSSMAMISGLSGRKSST | ||||||
Compositional bias | 999-1015 | Polar residues | ||||
Sequence: LSGRKSSTGSPTSPLTA | ||||||
Region | 999-1019 | Disordered | ||||
Sequence: LSGRKSSTGSPTSPLTAERLE | ||||||
Domain | 1041-1130 | Ig-like C2-type 3 | ||||
Sequence: PYFSKTIRDLEVVEGSAARFDCKIEGYPDPEVVWFKDDQSIRESRHFQIDYDEDGNCSLIISDVCGDDDAKYTCKAVNSLGEATCTAELI |
Sequence similarities
Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence & Isoform
- Sequence statusComplete
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.
- Name1
- SynonymsSmooth-muscle
- Length1,147
- Mass (Da)125,720
- Last updated1998-07-15 v2
- ChecksumF039E624C6E31024
P29294-3
- Name3
- SynonymsTelokin
- NoteHas no catalytic activity.
- Differences from canonical
- 1-992: Missing
Features
Showing features for alternative sequence, compositional bias, sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Alternative sequence | VSP_018849 | 1-992 | in isoform 3 | |||
Sequence: Missing | ||||||
Compositional bias | 13-27 | Basic and acidic residues | ||||
Sequence: PKTVSEEERKVHSPQ | ||||||
Compositional bias | 290-317 | Basic and acidic residues | ||||
Sequence: PKPAGKEELKKEVQNDVNCKREKAGAAD | ||||||
Compositional bias | 999-1015 | Polar residues | ||||
Sequence: LSGRKSSTGSPTSPLTA | ||||||
Sequence conflict | 1114 | in Ref. 3; AAA31409 | ||||
Sequence: C → R |
Keywords
- Coding sequence diversity
- Technical term