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Protein

Myosin light chain kinase, smooth muscle

Gene

MYLK

Organism
Bos taurus (Bovine)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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).By similarity1 Publication

Catalytic activityi

ATP + [myosin light-chain] = ADP + [myosin light-chain] phosphate.

Cofactori

Protein has several cofactor binding sites:

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei754 – 7541ATPPROSITE-ProRule annotation
Active sitei846 – 8461Proton acceptorPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi731 – 7399ATPPROSITE-ProRule annotation

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Ligandi

Actin-binding, ATP-binding, Calcium, Calmodulin-binding, Magnesium, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.11.18. 908.

Names & Taxonomyi

Protein namesi
Recommended name:
Myosin light chain kinase, smooth muscle (EC:2.7.11.18)
Short name:
MLCK
Short name:
smMLCK
Alternative name(s):
Telokin
Cleaved into the following chain:
Gene namesi
Name:MYLK
OrganismiBos taurus (Bovine)
Taxonomic identifieri9913 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaRuminantiaPecoraBovidaeBovinaeBos
Proteomesi
  • UP000009136 Componenti: Unplaced

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell projection, Cytoplasm, Cytoskeleton

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 11761176Myosin light chain kinase, smooth musclePRO_0000024352Add
BLAST
Chaini1 – 11711171Myosin light chain kinase, smooth muscle, deglutamylated formBy similarityPRO_0000403730Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei202 – 2021PhosphoserineBy similarity
Disulfide bondi377 ↔ 428PROSITE-ProRule annotation
Modified residuei699 – 6991PhosphoserineBy similarity
Modified residuei710 – 7101Phosphotyrosine; by ABL1By similarity
Modified residuei836 – 8361Phosphotyrosine; by ABL1By similarity
Modified residuei896 – 8961Phosphotyrosine; by ABL1By similarity
Modified residuei1020 – 10201PhosphoserineBy similarity
Modified residuei1021 – 10211PhosphoserineBy similarity
Modified residuei1033 – 10331PhosphoserineBy similarity
Modified residuei1034 – 10341PhosphoserineBy similarity
Modified residuei1037 – 10371PhosphoserineBy similarity
Modified residuei1039 – 10391PhosphothreonineBy similarity
Modified residuei1040 – 10401PhosphoserineBy similarity
Disulfide bondi1090 ↔ 1142PROSITE-ProRule annotation

Post-translational modificationi

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).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).By similarity

Keywords - PTMi

Disulfide bond, Phosphoprotein

Proteomic databases

PeptideAtlasiQ28824.
PRIDEiQ28824.

Interactioni

Subunit structurei

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).By similarity

Structurei

3D structure databases

ProteinModelPortaliQ28824.
SMRiQ28824. Positions 498-598, 720-987, 1060-1162.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Repeati100 – 111121Add
BLAST
Repeati112 – 123122Add
BLAST
Repeati124 – 135123Add
BLAST
Repeati136 – 147124Add
BLAST
Repeati148 – 159125Add
BLAST
Repeati160 – 171126Add
BLAST
Repeati172 – 183127Add
BLAST
Repeati184 – 195128Add
BLAST
Repeati196 – 207129Add
BLAST
Repeati208 – 2191210Add
BLAST
Repeati220 – 2311211Add
BLAST
Repeati232 – 2431212Add
BLAST
Repeati244 – 2551213Add
BLAST
Repeati256 – 2671214Add
BLAST
Repeati268 – 2791215Add
BLAST
Repeati280 – 2911216Add
BLAST
Domaini356 – 44489Ig-like C2-type 1Add
BLAST
Domaini498 – 58689Ig-like C2-type 2Add
BLAST
Domaini594 – 68693Fibronectin type-IIIPROSITE-ProRule annotationAdd
BLAST
Domaini725 – 980256Protein kinasePROSITE-ProRule annotationAdd
BLAST
Domaini1069 – 115890Ig-like C2-type 3Add
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 4141Actin-binding (calcium/calmodulin-sensitive)Add
BLAST
Regioni26 – 4116Calmodulin-bindingAdd
BLAST
Regioni100 – 29119216 X 12 AA tandem repeatsAdd
BLAST
Regioni319 – 721403Actin-binding (calcium/calmodulin-insensitive)Add
BLAST
Regioni972 – 103564Calmodulin-bindingAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi1171 – 11766Poly-Glu

Sequence similaritiesi

Contains 1 fibronectin type-III domain.PROSITE-ProRule annotation
Contains 1 protein kinase domain.PROSITE-ProRule annotation

Keywords - Domaini

Immunoglobulin domain, Repeat

Phylogenomic databases

HOGENOMiHOG000233016.
HOVERGENiHBG052550.
InParanoidiQ28824.
KOiK00907.

Family and domain databases

Gene3Di2.60.40.10. 5 hits.
InterProiIPR003961. FN3_dom.
IPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR013098. Ig_I-set.
IPR003599. Ig_sub.
IPR003598. Ig_sub2.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
IPR015725. Telokin/Myosin_light_ch_kin.
[Graphical view]
PANTHERiPTHR10489:SF700. PTHR10489:SF700. 1 hit.
PfamiPF00041. fn3. 1 hit.
PF07679. I-set. 3 hits.
PF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00060. FN3. 1 hit.
SM00409. IG. 3 hits.
SM00408. IGc2. 3 hits.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF48726. SSF48726. 3 hits.
SSF49265. SSF49265. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEiPS50853. FN3. 1 hit.
PS50835. IG_LIKE. 3 hits.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 3 isoformsi produced by alternative initiation. AlignAdd to basket

Note: At least 3 isoforms are produced by alternative initiation. Isoform Non-muscle is the longest.

Isoform Smooth-muscle (identifier: Q28824-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MDFRANLQRQ VKPKTLSEEE RKVHGPQQVD FRSVLAKKGT PKTPVPEKVP
60 70 80 90 100
PPKPATPDFR SVLGSKKKLP TENGSNNTEA LNAKAAEGLK PVGNAQPSGF
110 120 130 140 150
LKPVGNAKLA DTPKPLSSTK PAETPKPLGN VKPAETPKPL GSTKPAETPK
160 170 180 190 200
PLGSTKPAET PKPLGNVKPA ETPKPLGNIK PTETPKPLGS TKPAETPKPL
210 220 230 240 250
GSTKPAETPK PLGNVKPAET PKPLGNVKPA ETPKPLGNVK PAETPKPVSN
260 270 280 290 300
AKPAETLKPV GNAKPAETPK PLSNVKPAET PKLVGNAKPA ETSKPLDNAK
310 320 330 340 350
PAEAPKPLGN AKPAEIPKPT GKEELKKEIK NDVNCKKGHA GATDSEKRPE
360 370 380 390 400
SRGTAPTFEE KLQDLHVAEG QKLLLQCRVS SDPPATITWT LNGKTLKTTK
410 420 430 440 450
FIVLSQEGSL CSVSIEKALP EDRGLYKCVA KNSAGQAESS CQVTVDVPDA
460 470 480 490 500
PTSENAKAPE MKARRPKSSL PPVLGTESDA TVKKKPAPKT PPKAAMPPQI
510 520 530 540 550
IQFPEDQKVR AGESVELFGK VAGTQPITCT WMKFRKQIQD SEHIKVENSE
560 570 580 590 600
QGSKLTIRAA RQEHCGCYTL LVENKLGSRQ AQVNLTVVDK PDPPAGTPCA
610 620 630 640 650
SDIRSSSLTL SWYGSSYDGG SAVQSYSVEI WDSVDKTWKE LATCRSTSFN
660 670 680 690 700
VQDLLPDREY KFRVRAINVY GTSEPSQESE LTALGEKPEE EPKDEVEVSD
710 720 730 740 750
DDEKEPEVDY RTVTVNTEQK VSDFYDIEER LGSGKFGQVF RLVEKKTGKI
760 770 780 790 800
WAGKFFKAYS AKEKENIRQE ISIMNCLHHP KLVQCVDAFE EKANIVMVLE
810 820 830 840 850
IVSGGELFER IIDEDFELTE RECIKYMKQI SEGVEYIHKQ GIVHLDLKPE
860 870 880 890 900
NIMCVNKTGT RIKLIDFGLA RRLENAGSLK VLFGTPEFVA PEVINYEPIG
910 920 930 940 950
YATDMWSIGV ICYILVSGLS PFMGDNDNET LANVTSATWD FDDEAFDEIS
960 970 980 990 1000
DDAKDFISNL LKKDMKNRLN CTQCLQHPWL MKDTKNMEAK KLSKDRMKKY
1010 1020 1030 1040 1050
MARRKWQKTG NAVRAIGRLS SMAMISGLSG RKSSTGSPTS PLNAEKLESE
1060 1070 1080 1090 1100
DVSQAFLEAV AEEKPHVKPY FSKTIRDLEV VEGSAARFDC KIEGYPDPEV
1110 1120 1130 1140 1150
VWFKDDQSIR ESRHFQIDYD EDGNCSLIIS DVCGDDDAKY TCKAVNSLGE
1160 1170
ATCTAELIVE TMEEGEGEGG EEEEEE
Length:1,176
Mass (Da):128,825
Last modified:November 1, 1996 - v1
Checksum:iF53DC6D4D42D4B97
GO
Isoform Non-muscle (identifier: Q28824-2)

Sequence is not available
Length:
Mass (Da):
Isoform Telokin (identifier: Q28824-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-1021: Missing.

Note: No catalytic activity.
Show »
Length:155
Mass (Da):17,027
Checksum:i38C59F1292FFE876
GO

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 10211021Missing in isoform Telokin. CuratedVSP_018844Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
S57131 mRNA. Translation: AAB25794.1.
PIRiJN0583.
RefSeqiNP_788809.1. NM_176636.2. [Q28824-1]
UniGeneiBt.39894.

Genome annotation databases

GeneIDi338037.
KEGGibta:338037.

Keywords - Coding sequence diversityi

Alternative initiation

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
S57131 mRNA. Translation: AAB25794.1.
PIRiJN0583.
RefSeqiNP_788809.1. NM_176636.2. [Q28824-1]
UniGeneiBt.39894.

3D structure databases

ProteinModelPortaliQ28824.
SMRiQ28824. Positions 498-598, 720-987, 1060-1162.
ModBaseiSearch...
MobiDBiSearch...

Proteomic databases

PeptideAtlasiQ28824.
PRIDEiQ28824.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi338037.
KEGGibta:338037.

Organism-specific databases

CTDi4638.

Phylogenomic databases

HOGENOMiHOG000233016.
HOVERGENiHBG052550.
InParanoidiQ28824.
KOiK00907.

Enzyme and pathway databases

BRENDAi2.7.11.18. 908.

Family and domain databases

Gene3Di2.60.40.10. 5 hits.
InterProiIPR003961. FN3_dom.
IPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR013098. Ig_I-set.
IPR003599. Ig_sub.
IPR003598. Ig_sub2.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
IPR015725. Telokin/Myosin_light_ch_kin.
[Graphical view]
PANTHERiPTHR10489:SF700. PTHR10489:SF700. 1 hit.
PfamiPF00041. fn3. 1 hit.
PF07679. I-set. 3 hits.
PF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00060. FN3. 1 hit.
SM00409. IG. 3 hits.
SM00408. IGc2. 3 hits.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF48726. SSF48726. 3 hits.
SSF49265. SSF49265. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEiPS50853. FN3. 1 hit.
PS50835. IG_LIKE. 3 hits.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

  1. "Isolation of cDNA for bovine stomach 155 kDa protein exhibiting myosin light chain kinase activity."
    Kobayashi H., Inoue A., Mikawa T., Kuwayama H., Hotta Y., Masaki T., Ebashi S.
    J. Biochem. 112:786-791(1992) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: Stomach.
  2. "A novel regulatory effect of myosin light chain kinase from smooth muscle on the ATP-dependent interaction between actin and myosin."
    Kohama K., Okagaki T., Hayakawa K., Lin Y., Ishikawa R., Shimmen T., Inoue A.
    Biochem. Biophys. Res. Commun. 184:1204-1211(1992) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  3. "The structure and function of the actin-binding domain of myosin light chain kinase of smooth muscle."
    Ye L.H., Hayakawa K., Kishi H., Imamura M., Nakamura A., Okagaki T., Takagi T., Iwata A., Tanaka T., Kohama K.
    J. Biol. Chem. 272:32182-32189(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: ACTIN-BINDING, CALMODULIN-BINDING.

Entry informationi

Entry nameiMYLK_BOVIN
AccessioniPrimary (citable) accession number: Q28824
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: November 1, 1996
Last modified: July 6, 2016
This is version 142 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.