MYLK_BOVIN
ID MYLK_BOVIN Reviewed; 1176 AA.
AC Q28824;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 172.
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;
GN Name=MYLK;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM SMOOTH-MUSCLE).
RC TISSUE=Stomach;
RX PubMed=1284247; DOI=10.1093/oxfordjournals.jbchem.a123976;
RA Kobayashi H., Inoue A., Mikawa T., Kuwayama H., Hotta Y., Masaki T.,
RA Ebashi S.;
RT "Isolation of cDNA for bovine stomach 155 kDa protein exhibiting myosin
RT light chain kinase activity.";
RL J. Biochem. 112:786-791(1992).
RN [2]
RP FUNCTION.
RX PubMed=1534225; DOI=10.1016/s0006-291x(05)80010-5;
RA Kohama K., Okagaki T., Hayakawa K., Lin Y., Ishikawa R., Shimmen T.,
RA Inoue A.;
RT "A novel regulatory effect of myosin light chain kinase from smooth muscle
RT on the ATP-dependent interaction between actin and myosin.";
RL Biochem. Biophys. Res. Commun. 184:1204-1211(1992).
RN [3]
RP ACTIN-BINDING, AND CALMODULIN-BINDING.
RX PubMed=9405419; DOI=10.1074/jbc.272.51.32182;
RA Ye L.H., Hayakawa K., Kishi H., Imamura M., Nakamura A., Okagaki T.,
RA Takagi T., Iwata A., Tanaka T., Kohama K.;
RT "The structure and function of the actin-binding domain of myosin light
RT chain kinase of smooth muscle.";
RL J. Biol. Chem. 272:32182-32189(1997).
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 ECO:0000269|PubMed:1534225}.
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=Smooth-muscle;
CC IsoId=Q28824-1; Sequence=Displayed;
CC Name=Telokin;
CC IsoId=Q28824-3; Sequence=VSP_018844;
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 Telokin]: 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; S57131; AAB25794.1; -; mRNA.
DR PIR; JN0583; JN0583.
DR RefSeq; NP_788809.1; NM_176636.2. [Q28824-1]
DR AlphaFoldDB; Q28824; -.
DR SMR; Q28824; -.
DR STRING; 9913.ENSBTAP00000019385; -.
DR PeptideAtlas; Q28824; -.
DR PRIDE; Q28824; -.
DR Ensembl; ENSBTAT00000086177; ENSBTAP00000059804; ENSBTAG00000014567. [Q28824-1]
DR GeneID; 338037; -.
DR KEGG; bta:338037; -.
DR CTD; 4638; -.
DR VEuPathDB; HostDB:ENSBTAG00000014567; -.
DR eggNOG; KOG0613; Eukaryota.
DR GeneTree; ENSGT00940000157879; -.
DR InParanoid; Q28824; -.
DR OMA; TCLPVHL; -.
DR OrthoDB; 330091at2759; -.
DR BRENDA; 2.7.11.18; 908.
DR Proteomes; UP000009136; Chromosome 1.
DR Bgee; ENSBTAG00000014567; Expressed in myometrium and 107 other tissues.
DR ExpressionAtlas; Q28824; baseline and differential.
DR GO; GO:0032154; C:cleavage furrow; IBA:GO_Central.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0030027; C:lamellipodium; IBA:GO_Central.
DR GO; GO:0001725; C:stress fiber; IBA:GO_Central.
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; IBA:GO_Central.
DR GO; GO:0004672; F:protein kinase activity; IBA:GO_Central.
DR GO; GO:0006468; P:protein phosphorylation; IEA:InterPro.
DR GO; GO:0014820; P:tonic smooth muscle contraction; IBA:GO_Central.
DR CDD; cd00063; FN3; 1.
DR CDD; cd14191; STKc_MLCK1; 1.
DR Gene3D; 2.60.40.10; -; 4.
DR InterPro; IPR003961; FN3_dom.
DR InterPro; IPR036116; FN3_sf.
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; IPR015725; MLCK1_kinase_dom.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR Pfam; PF00041; fn3; 1.
DR Pfam; PF07679; I-set; 3.
DR Pfam; PF00069; Pkinase; 1.
DR SMART; SM00060; FN3; 1.
DR SMART; SM00409; IG; 3.
DR SMART; SM00408; IGc2; 3.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF48726; SSF48726; 3.
DR SUPFAM; SSF49265; SSF49265; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS50853; FN3; 1.
DR PROSITE; PS50835; IG_LIKE; 3.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE 1: Evidence at protein 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; Repeat;
KW Serine/threonine-protein kinase; Transferase.
FT CHAIN 1..1176
FT /note="Myosin light chain kinase, smooth muscle"
FT /id="PRO_0000024352"
FT CHAIN 1..1171
FT /note="Myosin light chain kinase, smooth muscle,
FT deglutamylated form"
FT /evidence="ECO:0000250"
FT /id="PRO_0000403730"
FT REPEAT 100..111
FT /note="1"
FT REPEAT 112..123
FT /note="2"
FT REPEAT 124..135
FT /note="3"
FT REPEAT 136..147
FT /note="4"
FT REPEAT 148..159
FT /note="5"
FT REPEAT 160..171
FT /note="6"
FT REPEAT 172..183
FT /note="7"
FT REPEAT 184..195
FT /note="8"
FT REPEAT 196..207
FT /note="9"
FT REPEAT 208..219
FT /note="10"
FT REPEAT 220..231
FT /note="11"
FT REPEAT 232..243
FT /note="12"
FT REPEAT 244..255
FT /note="13"
FT REPEAT 256..267
FT /note="14"
FT REPEAT 268..279
FT /note="15"
FT REPEAT 280..291
FT /note="16"
FT DOMAIN 356..444
FT /note="Ig-like C2-type 1"
FT DOMAIN 498..586
FT /note="Ig-like C2-type 2"
FT DOMAIN 594..686
FT /note="Fibronectin type-III"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT DOMAIN 725..980
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 1069..1158
FT /note="Ig-like C2-type 3"
FT REGION 1..354
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1..41
FT /note="Actin-binding (calcium/calmodulin-sensitive)"
FT REGION 26..41
FT /note="Calmodulin-binding"
FT REGION 100..291
FT /note="16 X 12 AA tandem repeats"
FT REGION 319..721
FT /note="Actin-binding (calcium/calmodulin-insensitive)"
FT REGION 448..497
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 673..707
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 972..1035
FT /note="Calmodulin-binding"
FT COMPBIAS 13..27
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 68..82
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 317..354
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 846
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 731..739
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 754
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 202
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q6PDN3"
FT MOD_RES 699
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q15746"
FT MOD_RES 710
FT /note="Phosphotyrosine; by ABL1"
FT /evidence="ECO:0000250|UniProtKB:Q15746"
FT MOD_RES 836
FT /note="Phosphotyrosine; by ABL1"
FT /evidence="ECO:0000250|UniProtKB:Q15746"
FT MOD_RES 896
FT /note="Phosphotyrosine; by ABL1"
FT /evidence="ECO:0000250|UniProtKB:Q15746"
FT MOD_RES 1020
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q6PDN3"
FT MOD_RES 1021
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q6PDN3"
FT MOD_RES 1033
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q15746"
FT MOD_RES 1034
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q6PDN3"
FT MOD_RES 1037
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q15746"
FT MOD_RES 1039
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q6PDN3"
FT MOD_RES 1040
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q15746"
FT DISULFID 377..428
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 1090..1142
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT VAR_SEQ 1..1021
FT /note="Missing (in isoform Telokin)"
FT /evidence="ECO:0000305"
FT /id="VSP_018844"
SQ SEQUENCE 1176 AA; 128825 MW; F53DC6D4D42D4B97 CRC64;
MDFRANLQRQ VKPKTLSEEE RKVHGPQQVD FRSVLAKKGT PKTPVPEKVP PPKPATPDFR
SVLGSKKKLP TENGSNNTEA LNAKAAEGLK PVGNAQPSGF LKPVGNAKLA DTPKPLSSTK
PAETPKPLGN VKPAETPKPL GSTKPAETPK PLGSTKPAET PKPLGNVKPA ETPKPLGNIK
PTETPKPLGS TKPAETPKPL GSTKPAETPK PLGNVKPAET PKPLGNVKPA ETPKPLGNVK
PAETPKPVSN AKPAETLKPV GNAKPAETPK PLSNVKPAET PKLVGNAKPA ETSKPLDNAK
PAEAPKPLGN AKPAEIPKPT GKEELKKEIK NDVNCKKGHA GATDSEKRPE SRGTAPTFEE
KLQDLHVAEG QKLLLQCRVS SDPPATITWT LNGKTLKTTK FIVLSQEGSL CSVSIEKALP
EDRGLYKCVA KNSAGQAESS CQVTVDVPDA PTSENAKAPE MKARRPKSSL PPVLGTESDA
TVKKKPAPKT PPKAAMPPQI IQFPEDQKVR AGESVELFGK VAGTQPITCT WMKFRKQIQD
SEHIKVENSE QGSKLTIRAA RQEHCGCYTL LVENKLGSRQ AQVNLTVVDK PDPPAGTPCA
SDIRSSSLTL SWYGSSYDGG SAVQSYSVEI WDSVDKTWKE LATCRSTSFN VQDLLPDREY
KFRVRAINVY GTSEPSQESE LTALGEKPEE EPKDEVEVSD DDEKEPEVDY RTVTVNTEQK
VSDFYDIEER LGSGKFGQVF RLVEKKTGKI WAGKFFKAYS AKEKENIRQE ISIMNCLHHP
KLVQCVDAFE EKANIVMVLE IVSGGELFER IIDEDFELTE RECIKYMKQI SEGVEYIHKQ
GIVHLDLKPE NIMCVNKTGT RIKLIDFGLA RRLENAGSLK VLFGTPEFVA PEVINYEPIG
YATDMWSIGV ICYILVSGLS PFMGDNDNET LANVTSATWD FDDEAFDEIS DDAKDFISNL
LKKDMKNRLN CTQCLQHPWL MKDTKNMEAK KLSKDRMKKY MARRKWQKTG NAVRAIGRLS
SMAMISGLSG RKSSTGSPTS PLNAEKLESE DVSQAFLEAV AEEKPHVKPY FSKTIRDLEV
VEGSAARFDC KIEGYPDPEV VWFKDDQSIR ESRHFQIDYD EDGNCSLIIS DVCGDDDAKY
TCKAVNSLGE ATCTAELIVE TMEEGEGEGG EEEEEE
