MYLK_SHEEP
ID MYLK_SHEEP Reviewed; 438 AA.
AC O02827;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1997, sequence version 1.
DT 03-AUG-2022, entry version 137.
DE RecName: Full=Myosin light chain kinase, smooth muscle;
DE Short=MLCK;
DE Short=smMLCK;
DE EC=2.7.11.18;
DE AltName: Full=Telokin;
DE Contains:
DE RecName: Full=Myosin light chain kinase, smooth muscle, deglutamylated form;
DE Flags: Fragment;
GN Name=MYLK;
OS Ovis aries (Sheep).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Caprinae; Ovis.
OX NCBI_TaxID=9940;
RN [1]
RP PARTIAL NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=8569750; DOI=10.1007/bf01076564;
RA Pato M.D., Kerc E., Lye S.J.;
RT "Phosphorylation and partial sequence of pregnant sheep myometrium myosin
RT light chain kinase.";
RL Mol. Cell. Biochem. 149:59-65(1995).
CC -!- FUNCTION: Calcium/calmodulin-dependent myosin light chain kinase
CC implicated in smooth muscle contraction via phosphorylation of myosin
CC light chains (MLC). Also regulates actin-myosin interaction through a
CC non-kinase activity. Phosphorylates PTK2B/PYK2 and myosin light-chains.
CC Involved in the inflammatory response (e.g. apoptosis, vascular
CC permeability, leukocyte diapedesis), cell motility and morphology,
CC airway hyperreactivity and other activities relevant to asthma.
CC Required for tonic airway smooth muscle contraction that is necessary
CC for physiological and asthmatic airway resistance. Necessary for
CC gastrointestinal motility. Implicated in the regulation of endothelial
CC as well as vascular permeability, probably via the regulation of
CC cytoskeletal rearrangements. In the nervous system it has been shown to
CC control the growth initiation of astrocytic processes in culture and to
CC participate in transmitter release at synapses formed between cultured
CC sympathetic ganglion cells. Critical participant in signaling sequences
CC that result in fibroblast apoptosis. Plays a role in the regulation of
CC epithelial cell survival. Required for epithelial wound healing,
CC especially during actomyosin ring contraction during purse-string wound
CC closure. Mediates RhoA-dependent membrane blebbing. Triggers TRPC5
CC channel activity in a calcium-dependent signaling, by inducing its
CC subcellular localization at the plasma membrane. Promotes cell
CC migration (including tumor cells) and tumor metastasis. PTK2B/PYK2
CC activation by phosphorylation mediates ITGB2 activation and is thus
CC essential to trigger neutrophil transmigration during acute lung injury
CC (ALI). May regulate optic nerve head astrocyte migration. Probably
CC involved in mitotic cytoskeletal regulation. Regulates tight junction
CC probably by modulating ZO-1 exchange in the perijunctional actomyosin
CC ring. Mediates burn-induced microvascular barrier injury; triggers
CC endothelial contraction in the development of microvascular
CC hyperpermeability by phosphorylating MLC. Essential for intestinal
CC barrier dysfunction. Mediates Giardia spp.-mediated reduced epithelial
CC barrier function during giardiasis intestinal infection via
CC reorganization of cytoskeletal F-actin and tight junctional ZO-1.
CC Necessary for hypotonicity-induced Ca(2+) entry and subsequent
CC activation of volume-sensitive organic osmolyte/anion channels (VSOAC)
CC in cervical cancer cells (By similarity). {ECO:0000250}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[myosin light chain] = ADP + H(+) + O-phospho-L-
CC seryl-[myosin light chain]; Xref=Rhea:RHEA:22004, Rhea:RHEA-
CC COMP:13684, Rhea:RHEA-COMP:13685, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:29999, ChEBI:CHEBI:30616, ChEBI:CHEBI:83421,
CC ChEBI:CHEBI:456216; EC=2.7.11.18;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[myosin light chain] = ADP + H(+) + O-
CC phospho-L-threonyl-[myosin light chain]; Xref=Rhea:RHEA:53900,
CC Rhea:RHEA-COMP:13686, Rhea:RHEA-COMP:13687, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30013, ChEBI:CHEBI:30616, ChEBI:CHEBI:61977,
CC ChEBI:CHEBI:456216; EC=2.7.11.18;
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250};
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108; Evidence={ECO:0000250};
CC -!- SUBUNIT: All isoforms including Telokin bind calmodulin. Interacts with
CC SVIL (By similarity). Interacts with CTTN; this interaction is reduced
CC during thrombin-induced endothelial cell (EC) contraction but is
CC promoted by the barrier-protective agonist sphingosine 1-phosphate
CC (S1P) within lamellipodia. A complex made of ABL1, CTTN and MYLK
CC regulates cortical actin-based cytoskeletal rearrangement critical to
CC sphingosine 1-phosphate (S1P)-mediated endothelial cell (EC) barrier
CC enhancement. Binds to NAA10/ARD1 and PTK2B/PYK2 (By similarity).
CC {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q15746}. Cell
CC projection, lamellipodium {ECO:0000250|UniProtKB:Q15746}. Cleavage
CC furrow {ECO:0000250|UniProtKB:Q15746}. Cytoplasm, cytoskeleton, stress
CC fiber {ECO:0000250|UniProtKB:Q15746}. Note=Localized to stress fibers
CC during interphase and to the cleavage furrow during mitosis.
CC {ECO:0000250|UniProtKB:Q15746}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative promoter usage; Named isoforms=2;
CC Name=1; Synonyms=Smooth-muscle;
CC IsoId=O02827-1; Sequence=Displayed;
CC Name=2; Synonyms=Telokin;
CC IsoId=O02827-2; Sequence=VSP_018850;
CC -!- PTM: The C-terminus is deglutamylated by AGTPBP1/CCP1, AGBL1/CCP4 and
CC AGBL4/CCP6, leading to the formation of Myosin light chain kinase,
CC smooth muscle, deglutamylated form. The consequences of C-terminal
CC deglutamylation are unknown (By similarity). {ECO:0000250}.
CC -!- PTM: Can probably be down-regulated by phosphorylation. Tyrosine
CC phosphorylation by ABL1 increases kinase activity, reverses MLCK-
CC mediated inhibition of Arp2/3-mediated actin polymerization, and
CC enhances CTTN-binding. Phosphorylation by SRC promotes CTTN binding (By
CC similarity). {ECO:0000250}.
CC -!- MISCELLANEOUS: [Isoform 2]: Has no catalytic activity. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CAMK Ser/Thr
CC protein kinase family. {ECO:0000305}.
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DR EMBL; S80867; AAB50715.2; -; mRNA.
DR STRING; 9940.ENSOARP00000021691; -.
DR PRIDE; O02827; -.
DR eggNOG; KOG0613; Eukaryota.
DR BRENDA; 2.7.11.18; 2668.
DR Proteomes; UP000002356; Unplaced.
DR GO; GO:0032154; C:cleavage furrow; IEA:UniProtKB-SubCell.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005856; C:cytoskeleton; IEA:UniProtKB-SubCell.
DR GO; GO:0030027; C:lamellipodium; IEA:UniProtKB-SubCell.
DR GO; GO:0003779; F:actin binding; IEA:UniProtKB-KW.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0005516; F:calmodulin binding; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004687; F:myosin light chain kinase activity; IEA:UniProtKB-EC.
DR GO; GO:0006468; P:protein phosphorylation; IEA:InterPro.
DR Gene3D; 2.60.40.10; -; 1.
DR InterPro; IPR007110; Ig-like_dom.
DR InterPro; IPR036179; Ig-like_dom_sf.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR013098; Ig_I-set.
DR InterPro; IPR003599; Ig_sub.
DR InterPro; IPR003598; Ig_sub2.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR Pfam; PF07679; I-set; 1.
DR Pfam; PF00069; Pkinase; 1.
DR SMART; SM00409; IG; 1.
DR SMART; SM00408; IGc2; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF48726; SSF48726; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS50835; IG_LIKE; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE 2: Evidence at transcript level;
KW Actin-binding; Alternative promoter usage; ATP-binding; Calcium;
KW Calmodulin-binding; Cell projection; Cytoplasm; Cytoskeleton;
KW Disulfide bond; Immunoglobulin domain; Kinase; Magnesium; Metal-binding;
KW Nucleotide-binding; Phosphoprotein; Reference proteome;
KW Serine/threonine-protein kinase; Transferase.
FT CHAIN <1..438
FT /note="Myosin light chain kinase, smooth muscle"
FT /id="PRO_0000024359"
FT CHAIN <1..433
FT /note="Myosin light chain kinase, smooth muscle,
FT deglutamylated form"
FT /evidence="ECO:0000250"
FT /id="PRO_0000403734"
FT DOMAIN <1..241
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 331..420
FT /note="Ig-like C2-type"
FT REGION 233..296
FT /note="Calmodulin-binding"
FT REGION 283..438
FT /note="Telokin"
FT ACT_SITE 107
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 15
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 97
FT /note="Phosphotyrosine; by ABL1"
FT /evidence="ECO:0000250|UniProtKB:Q15746"
FT MOD_RES 157
FT /note="Phosphotyrosine; by ABL1"
FT /evidence="ECO:0000250|UniProtKB:Q15746"
FT MOD_RES 281
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q6PDN3"
FT MOD_RES 282
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q6PDN3"
FT MOD_RES 294
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q15746"
FT MOD_RES 295
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q6PDN3"
FT MOD_RES 298
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q15746"
FT MOD_RES 300
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q6PDN3"
FT MOD_RES 301
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q15746"
FT DISULFID 352..404
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT VAR_SEQ <1..282
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_018850"
FT NON_TER 1
SQ SEQUENCE 438 AA; 49507 MW; 77A02F4885A10B51 CRC64;
FRLVEKKTGK VWAGKFFKAY SAKEKENIRQ EISIMNCLHH PKLVQCVDAF EEKANIVMVL
EIVSGGELFE RIIDEDFELT ERECIKYMKQ ISEGVEYIHK QGIVHLDLKP ENIMCVNKTG
TRIKLIDFGL ARRLENAGSL KVLFGTPEFV APEVINYEPI GYATDMWSIG VICYILVSGL
SPFMGDNDNE TLANVTSATW DFDDEAFDEI SDDAKDFISN LLKKDIKNRL NCTQCLQHPW
LXXXTKNMEA KKLSKHRMKK YMARRKWQKT GNAVRAIGRL SSMAMISGLS GRKSSTGSPT
SPLNAEKLES EEDVSQAFLE AVAEEKPHVK PYFSKTIRDL EVVEGSAARF DCKIEGYPDP
EVVWFKDDQS IRESRHFQID YQEDGNCSLI ISDVCGDDDA KYTCKAVNSL GEATCTAELI
VETMEEGEGE GGEEEEEE
