MYLK3_MOUSE
ID MYLK3_MOUSE Reviewed; 795 AA.
AC Q3UIZ8; B0LY41; Q3V3V0; Q8BWD1;
DT 23-JAN-2007, integrated into UniProtKB/Swiss-Prot.
DT 11-OCT-2005, sequence version 1.
DT 03-AUG-2022, entry version 133.
DE RecName: Full=Myosin light chain kinase 3;
DE EC=2.7.11.18 {ECO:0000269|PubMed:17885681, ECO:0000269|PubMed:18202317};
DE AltName: Full=Cardiac MyBP-C-associated Ca/CaM kinase;
DE Short=Cardiac MLCK {ECO:0000303|PubMed:17885681, ECO:0000303|PubMed:18202317};
GN Name=Mylk3;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, CATALYTIC ACTIVITY,
RP BIOPHYSICOCHEMICAL PROPERTIES, SUBCELLULAR LOCATION, TISSUE SPECIFICITY,
RP DEVELOPMENTAL STAGE, AND PHOSPHORYLATION.
RC TISSUE=Heart;
RX PubMed=18202317; DOI=10.1161/circresaha.107.161687;
RA Chan J.Y., Takeda M., Briggs L.E., Graham M.L., Lu J.T., Horikoshi N.,
RA Weinberg E.O., Aoki H., Sato N., Chien K.R., Kasahara H.;
RT "Identification of cardiac-specific myosin light chain kinase.";
RL Circ. Res. 102:571-580(2008).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC STRAIN=C57BL/6J; TISSUE=Heart, and Testis;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=17885681; DOI=10.1172/jci30804;
RA Seguchi O., Takashima S., Yamazaki S., Asakura M., Asano Y., Shintani Y.,
RA Wakeno M., Minamino T., Kondo H., Furukawa H., Nakamaru K., Naito A.,
RA Takahashi T., Ohtsuka T., Kawakami K., Isomura T., Kitamura S., Tomoike H.,
RA Mochizuki N., Kitakaze M.;
RT "A cardiac myosin light chain kinase regulates sarcomere assembly in the
RT vertebrate heart.";
RL J. Clin. Invest. 117:2812-2824(2007).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-432, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Heart, and Spleen;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
CC -!- FUNCTION: Kinase that phosphorylates MYL2 in vitro (PubMed:18202317,
CC PubMed:17885681). Has been proposed to be calmodulin-dependent
CC (PubMed:17885681), although MYL2 phosphorylation has also been observed
CC in the presence or absence of calmodulin (PubMed:18202317). Promotes
CC sarcomere formation in cardiomyocytes and increases cardiomyocyte
CC contractility (By similarity). {ECO:0000250|UniProtKB:E9PT87,
CC ECO:0000269|PubMed:17885681, ECO:0000269|PubMed:18202317}.
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 Evidence={ECO:0000305|PubMed:17885681, ECO:0000305|PubMed:18202317};
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 Evidence={ECO:0000305|PubMed:17885681, ECO:0000305|PubMed:18202317};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=4.3 uM for MYL2 {ECO:0000269|PubMed:18202317};
CC Vmax=0.26 umol/min/mg enzyme {ECO:0000269|PubMed:18202317};
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:18202317}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q3UIZ8-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q3UIZ8-2; Sequence=VSP_022369, VSP_022370;
CC -!- TISSUE SPECIFICITY: Restricted to cardiomyocytes (at protein level).
CC Down-regulated in heart after experimental myocardial infarction at the
CC protein level; no significant changes at the mRNA level.
CC {ECO:0000269|PubMed:18202317}.
CC -!- DEVELOPMENTAL STAGE: Up-regulated in the heart from 10.5 dpc to
CC neonates and further increased in adults. Down-regulated in aged hearts
CC (at protein level). {ECO:0000269|PubMed:18202317}.
CC -!- PTM: Phosphorylated on serine residues. {ECO:0000269|PubMed:18202317}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CAMK Ser/Thr
CC protein kinase family. {ECO:0000305}.
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DR EMBL; EU403565; ABY89726.1; -; mRNA.
DR EMBL; AK031546; BAE43277.1; -; mRNA.
DR EMBL; AK052858; BAC35177.1; -; mRNA.
DR EMBL; AK146683; BAE27357.1; -; mRNA.
DR CCDS; CCDS40422.1; -. [Q3UIZ8-1]
DR RefSeq; NP_001284541.1; NM_001297612.1.
DR RefSeq; NP_780650.2; NM_175441.5. [Q3UIZ8-1]
DR AlphaFoldDB; Q3UIZ8; -.
DR SMR; Q3UIZ8; -.
DR IntAct; Q3UIZ8; 1.
DR STRING; 10090.ENSMUSP00000034133; -.
DR iPTMnet; Q3UIZ8; -.
DR PhosphoSitePlus; Q3UIZ8; -.
DR MaxQB; Q3UIZ8; -.
DR PaxDb; Q3UIZ8; -.
DR PRIDE; Q3UIZ8; -.
DR ProteomicsDB; 287573; -. [Q3UIZ8-1]
DR ProteomicsDB; 287574; -. [Q3UIZ8-2]
DR Antibodypedia; 28053; 270 antibodies from 26 providers.
DR DNASU; 213435; -.
DR Ensembl; ENSMUST00000034133; ENSMUSP00000034133; ENSMUSG00000031698. [Q3UIZ8-1]
DR Ensembl; ENSMUST00000121972; ENSMUSP00000113960; ENSMUSG00000031698. [Q3UIZ8-2]
DR GeneID; 213435; -.
DR KEGG; mmu:213435; -.
DR UCSC; uc009mps.1; mouse. [Q3UIZ8-1]
DR CTD; 91807; -.
DR MGI; MGI:2443063; Mylk3.
DR VEuPathDB; HostDB:ENSMUSG00000031698; -.
DR eggNOG; KOG0032; Eukaryota.
DR GeneTree; ENSGT00940000160007; -.
DR HOGENOM; CLU_000288_90_0_1; -.
DR InParanoid; Q3UIZ8; -.
DR OMA; DPWPLEE; -.
DR OrthoDB; 218222at2759; -.
DR PhylomeDB; Q3UIZ8; -.
DR TreeFam; TF314166; -.
DR BRENDA; 2.7.11.18; 3474.
DR SABIO-RK; Q3UIZ8; -.
DR BioGRID-ORCS; 213435; 1 hit in 75 CRISPR screens.
DR ChiTaRS; Mylk3; mouse.
DR PRO; PR:Q3UIZ8; -.
DR Proteomes; UP000000589; Chromosome 8.
DR RNAct; Q3UIZ8; protein.
DR Bgee; ENSMUSG00000031698; Expressed in myocardium of ventricle and 81 other tissues.
DR ExpressionAtlas; Q3UIZ8; baseline and differential.
DR Genevisible; Q3UIZ8; MM.
DR GO; GO:0005737; C:cytoplasm; IDA:BHF-UCL.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004683; F:calmodulin-dependent protein kinase activity; IDA:BHF-UCL.
DR GO; GO:0004687; F:myosin light chain kinase activity; IDA:BHF-UCL.
DR GO; GO:0055003; P:cardiac myofibril assembly; ISO:MGI.
DR GO; GO:0071347; P:cellular response to interleukin-1; ISO:MGI.
DR GO; GO:0060298; P:positive regulation of sarcomere organization; ISO:MGI.
DR GO; GO:0006468; P:protein phosphorylation; IDA:BHF-UCL.
DR GO; GO:0002528; P:regulation of vascular permeability involved in acute inflammatory response; ISO:MGI.
DR GO; GO:0045214; P:sarcomere organization; IDA:BHF-UCL.
DR GO; GO:0048769; P:sarcomerogenesis; ISO:MGI.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR Pfam; PF00069; Pkinase; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
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 Alternative splicing; ATP-binding; Cytoplasm; Kinase; Magnesium;
KW Nucleotide-binding; Phosphoprotein; Reference proteome;
KW Serine/threonine-protein kinase; Transferase.
FT CHAIN 1..795
FT /note="Myosin light chain kinase 3"
FT /id="PRO_0000272201"
FT DOMAIN 491..746
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 236..258
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 305..328
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 367..452
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 612
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 497..505
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 520
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 155
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:E9PT87"
FT MOD_RES 351
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:E9PT87"
FT MOD_RES 432
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT VAR_SEQ 100..162
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_022369"
FT VAR_SEQ 777..795
FT /note="KHFHVVTAVNRLRKFPTCP -> VFWVFFSKSCI (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_022370"
SQ SEQUENCE 795 AA; 86372 MW; 9B9874D50E6EBA20 CRC64;
MSGVSEEDPE GLAPQGLPAL GGACLATMDK KLNVLTEKVD RLLHFQEDVT EKLQCVCQGM
DHLEQDLHRL EASRELSLAG SGSTPPTTAQ AAWPEVLELV RAVRQEGAQH GARLEALFKM
VVAVDRAITL VGSTFQNSKV ADFIMQGTVP GRKGSLADGP EENKEQAEVA GVKPNHVLTT
GGVQADASRT LWEESQKEDI PVRTVEGLPL IINTSLKGAD LTQAGASLRQ GVEVLGPGQV
PLPTEAESRL PETASENTGA TLELSVAIDR ISEVLTSLKM SQGGGQETSS SKPDCWLSEE
AMRLSSGPLP QPLGPLTPDS DIHSGDALPR IPINMQEMAT PGELLETQSG SPIGSAEAPG
LGTVLEDQIP KGARPFPPLP KRSSNNGGMS AEEEIGSGAE PMRGPSLATR DWRDETVGTT
DLQQGIDPGA VSPEPGKDHA AQGPGRTEAG RLSSAAEAAI VVLDDSAAPP APFEHRVVSI
KDTLISAGYT VSQHEVLGGG RFGQVHRCTE RSTGLALAAK IIKVKNVKDR EDVKNEVNIM
NQLSHVNLIQ LYDAFESKSS FTLIMEYVDG GELFDRITDE KYHLTELDVV LFTRQICEGV
HYLHQHYILH LDLKPENILC VSQTGHQIKI IDFGLARRYK PREKLKVNFG TPEFLAPEVV
NYEFVSFPTD MWSVGVITYM LLSGLSPFLG ETDAETMNFI VNCSWDFDAD TFKGLSEEAK
DFVSRLLVKE KSCRMSATQC LKHEWLSHLP AKASGSNVRL RSQQLLQKYM AQSKWKKHFH
VVTAVNRLRK FPTCP
