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   24-JAN-2024, entry version 140.
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; 10090-ENSMUSP00000034133; -.
DR   ProteomicsDB; 287573; -. [Q3UIZ8-1]
DR   ProteomicsDB; 287574; -. [Q3UIZ8-2]
DR   Antibodypedia; 28053; 303 antibodies from 27 providers.
DR   DNASU; 213435; -.
DR   Ensembl; ENSMUST00000034133.14; ENSMUSP00000034133.8; ENSMUSG00000031698.15. [Q3UIZ8-1]
DR   Ensembl; ENSMUST00000121972.8; ENSMUSP00000113960.2; ENSMUSG00000031698.15. [Q3UIZ8-2]
DR   GeneID; 213435; -.
DR   KEGG; mmu:213435; -.
DR   UCSC; uc009mps.1; mouse. [Q3UIZ8-1]
DR   AGR; MGI:2443063; -.
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; IHVQEMD; -.
DR   OrthoDB; 5402680at2759; -.
DR   PhylomeDB; Q3UIZ8; -.
DR   TreeFam; TF314166; -.
DR   BRENDA; 2.7.11.18; 3474.
DR   SABIO-RK; Q3UIZ8; -.
DR   BioGRID-ORCS; 213435; 1 hit in 80 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 82 other cell types or tissues.
DR   ExpressionAtlas; Q3UIZ8; baseline and differential.
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   CDD; cd14192; STKc_MLCK3; 1.
DR   Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1.
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   PANTHER; PTHR24342:SF15; DEATH-ASSOCIATED PROTEIN KINASE 2; 1.
DR   PANTHER; PTHR24342; SERINE/THREONINE-PROTEIN KINASE 17; 1.
DR   Pfam; PF00069; Pkinase; 1.
DR   SMART; SM00220; S_TKc; 1.
DR   SUPFAM; SSF56112; Protein kinase-like (PK-like); 1.
DR   PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR   PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR   PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
DR   Genevisible; Q3UIZ8; MM.
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
//