| Tag | Content |
|---|
| CPLM ID | CPLM-012625 |
UniProt Accession | |
Genbank Protein ID | |
Genbank Nucleotide ID | |
Protein Name | Myosin light chain kinase, smooth muscle |
Protein Synonyms/Alias | MLCK; smMLCK; Kinase-related protein; KRP; Telokin; Myosin light chain kinase, smooth muscle, deglutamylated form |
Gene Name | MYLK |
Gene Synonyms/Alias | MLCK; MLCK1; MYLK1 |
Created Date | July 27, 2013 |
Organism | Homo sapiens (Human) |
NCBI Taxa ID | 9606 |
Lysine Modification | Position | Peptide | Type | References |
|---|
| 608 | HEKKSSRKSEYLLPV | acetylation | [1] | | 903 | DFRDLLGKKVSTKTL | ubiquitination | [2] |
|
Reference | [1] Arrest defective-1 controls tumor cell behavior by acetylating myosin light chain kinase. Shin DH, Chun YS, Lee KH, Shin HW, Park JW. PLoS One. 2009 Oct 14;4(10):e7451. [ PMID: 19826488] [2] Methods for quantification of in vivo changes in protein ubiquitination following proteasome and deubiquitinase inhibition. Udeshi ND, Mani DR, Eisenhaure T, Mertins P, Jaffe JD, Clauser KR, Hacohen N, Carr SA. Mol Cell Proteomics. 2012 May;11(5):148-59. [ PMID: 22505724] |
Functional Description | 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 Ca(2+) entry and subsequent activation of volume-sensitive organic osmolyte/anion channels (VSOAC) in cervical cancer cells. Responsible for high proliferative ability of breast cancer cells through anti-apoptosis. |
Sequence Annotation | DOMAIN 33 122 Ig-like C2-type 1.
DOMAIN 161 249 Ig-like C2-type 2.
DOMAIN 414 503 Ig-like C2-type 3.
DOMAIN 514 599 Ig-like C2-type 4.
DOMAIN 620 711 Ig-like C2-type 5.
DOMAIN 721 821 Ig-like C2-type 6.
REPEAT 868 895 1-1.
REPEAT 896 923 1-2.
REPEAT 924 951 1-3.
REPEAT 952 979 1-4.
REPEAT 980 998 1-5; truncated.
REPEAT 999 1003 2-1; truncated.
REPEAT 1004 1015 2-2.
REPEAT 1016 1027 2-3.
REPEAT 1028 1039 2-4.
REPEAT 1040 1051 2-5.
REPEAT 1052 1063 2-6.
DOMAIN 1098 1186 Ig-like C2-type 7.
DOMAIN 1238 1326 Ig-like C2-type 8.
DOMAIN 1331 1422 Fibronectin type-III.
DOMAIN 1464 1719 Protein kinase.
DOMAIN 1809 1898 Ig-like C2-type 9.
NP_BIND 1470 1478 ATP (By similarity).
REGION 868 998 5 X 28 AA approximate tandem repeats.
REGION 923 963 Actin-binding (calcium/calmodulin-
REGION 948 963 Calmodulin-binding (By similarity).
REGION 999 1063 6 X 12 AA approximate tandem repeats.
REGION 1061 1460 Actin-binding (calcium/calmodulin-
REGION 1711 1774 Calmodulin-binding.
ACT_SITE 1585 1585 Proton acceptor (By similarity).
BINDING 1493 1493 ATP (By similarity).
MOD_RES 231 231 Phosphotyrosine; by ABL1.
MOD_RES 343 343 Phosphoserine (By similarity).
MOD_RES 464 464 Phosphotyrosine; by ABL1 and SRC.
MOD_RES 471 471 Phosphotyrosine; by SRC.
MOD_RES 556 556 Phosphotyrosine; by ABL1.
MOD_RES 608 608 N6-acetyllysine.
MOD_RES 611 611 Phosphotyrosine; by ABL1.
MOD_RES 792 792 Phosphotyrosine; by ABL1.
MOD_RES 814 814 Phosphoserine (By similarity).
MOD_RES 846 846 Phosphotyrosine; by ABL1.
MOD_RES 1438 1438 Phosphoserine.
MOD_RES 1449 1449 Phosphotyrosine; by ABL1.
MOD_RES 1575 1575 Phosphotyrosine; by ABL1.
MOD_RES 1635 1635 Phosphotyrosine; by ABL1.
MOD_RES 1759 1759 Phosphoserine (By similarity).
MOD_RES 1776 1776 Phosphoserine (By similarity).
DISULFID 182 233 By similarity.
DISULFID 435 487 By similarity.
DISULFID 535 583 By similarity.
DISULFID 742 805 By similarity.
DISULFID 1119 1170 By similarity.
DISULFID 1830 1882 By similarity. |
Keyword | 3D-structure; Acetylation; Actin-binding; Alternative initiation; Alternative splicing; Aortic aneurysm; ATP-binding; Calcium; Calmodulin-binding; Cell projection; Complete proteome; Cytoplasm; Cytoskeleton; Direct protein sequencing; Disease mutation; Disulfide bond; Immunoglobulin domain; Kinase; Magnesium; Metal-binding; Nucleotide-binding; Phosphoprotein; Polymorphism; Reference proteome; Repeat; Serine/threonine-protein kinase; Transferase. |
Sequence Source | UniProt (SWISSPROT/TrEMBL); GenBank; EMBL |
Protein Length | 1914 AA |
Protein Sequence | MGDVKLVASS HISKTSLSVD PSRVDSMPLT EAPAFILPPR NLCIKEGATA KFEGRVRGYP 60
EPQVTWHRNG QPITSGGRFL LDCGIRGTFS LVIHAVHEED RGKYTCEATN GSGARQVTVE 120
LTVEGSFAKQ LGQPVVSKTL GDRFSAPAVE TRPSIWGECP PKFATKLGRV VVKEGQMGRF 180
SCKITGRPQP QVTWLKGNVP LQPSARVSVS EKNGMQVLEI HGVNQDDVGV YTCLVVNGSG 240
KASMSAELSI QGLDSANRSF VRETKATNSD VRKEVTNVIS KESKLDSLEA AAKSKNCSSP 300
QRGGSPPWAA NSQPQPPRES KLESCKDSPR TAPQTPVLQK TSSSITLQAA RVQPEPRAPG 360
LGVLSPSGEE RKRPAPPRPA TFPTRQPGLG SQDVVSKAAN RRIPMEGQRD SAFPKFESKP 420
QSQEVKENQT VKFRCEVSGI PKPEVAWFLE GTPVRRQEGS IEVYEDAGSH YLCLLKARTR 480
DSGTYSCTAS NAQGQLSCSW TLQVERLAVM EVAPSFSSVL KDCAVIEGQD FVLQCSVRGT 540
PVPRITWLLN GQPIQYARST CEAGVAELHI QDALPEDHGT YTCLAENALG QVSCSAWVTV 600
HEKKSSRKSE YLLPVAPSKP TAPIFLQGLS DLKVMDGSQV TMTVQVSGNP PPEVIWLHNG 660
NEIQESEDFH FEQRGTQHSL CIQEVFPEDT GTYTCEAWNS AGEVRTQAVL TVQEPHDGTQ 720
PWFISKPRSV TASLGQSVLI SCAIAGDPFP TVHWLRDGKA LCKDTGHFEV LQNEDVFTLV 780
LKKVQPWHAG QYEILLKNRV GECSCQVSLM LQNSSARALP RGREPASCED LCGGGVGADG 840
GGSDRYGSLR PGWPARGQGW LEEEDGEDVR GVLKRRVETR QHTEEAIRQQ EVEQLDFRDL 900
LGKKVSTKTL SEDDLKEIPA EQMDFRANLQ RQVKPKTVSE EERKVHSPQQ VDFRSVLAKK 960
GTSKTPVPEK VPPPKPATPD FRSVLGGKKK LPAENGSSSA ETLNAKAVES SKPLSNAQPS 1020
GPLKPVGNAK PAETLKPMGN AKPAETLKPM GNAKPDENLK SASKEELKKD VKNDVNCKRG 1080
HAGTTDNEKR SESQGTAPAF KQKLQDVHVA EGKKLLLQCQ VSSDPPATII WTLNGKTLKT 1140
TKFIILSQEG SLCSVSIEKA LPEDRGLYKC VAKNDAGQAE CSCQVTVDDA PASENTKAPE 1200
MKSRRPKSSL PPVLGTESDA TVKKKPAPKT PPKAAMPPQI IQFPEDQKVR AGESVELFGK 1260
VTGTQPITCT WMKFRKQIQE SEHMKVENSE NGSKLTILAA RQEHCGCYTL LVENKLGSRQ 1320
AQVNLTVVDK PDPPAGTPCA SDIRSSSLTL SWYGSSYDGG SAVQSYSIEI WDSANKTWKE 1380
LATCRSTSFN VQDLLPDHEY KFRVRAINVY GTSEPSQESE LTTVGEKPEE PKDEVEVSDD 1440
DEKEPEVDYR TVTINTEQKV SDFYDIEERL GSGKFGQVFR LVEKKTRKVW AGKFFKAYSA 1500
KEKENIRQEI SIMNCLHHPK LVQCVDAFEE KANIVMVLEI VSGGELFERI IDEDFELTER 1560
ECIKYMRQIS EGVEYIHKQG IVHLDLKPEN IMCVNKTGTR IKLIDFGLAR RLENAGSLKV 1620
LFGTPEFVAP EVINYEPIGY ATDMWSIGVI CYILVSGLSP FMGDNDNETL ANVTSATWDF 1680
DDEAFDEISD DAKDFISNLL KKDMKNRLDC TQCLQHPWLM KDTKNMEAKK LSKDRMKKYM 1740
ARRKWQKTGN AVRAIGRLSS MAMISGLSGR KSSTGSPTSP LNAEKLESEE DVSQAFLEAV 1800
AEEKPHVKPY FSKTIRDLEV VEGSAARFDC KIEGYPDPEV VWFKDDQSIR ESRHFQIDYD 1860
EDGNCSLIIS DVCGDDDAKY TCKAVNSLGE ATCTAELIVE TMEEGEGEGE EEEE 1914 |
Gene Ontology | GO:0032154; C:cleavage furrow; IDA:UniProtKB. GO:0005829; C:cytosol; TAS:Reactome. GO:0030027; C:lamellipodium; IDA:UniProtKB. GO:0005886; C:plasma membrane; IDA:HPA. GO:0001725; C:stress fiber; IDA:UniProtKB. GO:0005524; F:ATP binding; IEA:UniProtKB-KW. GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. GO:0004687; F:myosin light chain kinase activity; IDA:UniProtKB. GO:0060414; P:aorta smooth muscle tissue morphogenesis; IMP:BHF-UCL. GO:0032060; P:bleb assembly; IMP:UniProtKB. GO:0071476; P:cellular hypotonic response; IDA:UniProtKB. GO:0051928; P:positive regulation of calcium ion transport; IDA:UniProtKB. GO:0030335; P:positive regulation of cell migration; IDA:UniProtKB. GO:0090303; P:positive regulation of wound healing; IDA:UniProtKB. GO:0014820; P:tonic smooth muscle contraction; ISS:UniProtKB. |
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