MYLK3_RAT
ID MYLK3_RAT Reviewed; 786 AA.
AC E9PT87; A8WE96;
DT 03-OCT-2012, integrated into UniProtKB/Swiss-Prot.
DT 05-APR-2011, sequence version 1.
DT 03-AUG-2022, entry version 67.
DE RecName: Full=Myosin light chain kinase 3;
DE EC=2.7.11.18;
DE AltName: Full=Cardiac-MyBP-C-associated Ca/CaM kinase;
DE Short=Cardiac-MLCK;
GN Name=Mylk3;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, INDUCTION, AND TISSUE SPECIFICITY.
RC STRAIN=Wistar;
RX PubMed=20615916; DOI=10.1093/cvr/cvq223;
RA Gu X., Liu X., Xu D., Li X., Yan M., Qi Y., Yan W., Wang W., Pan J., Xu Y.,
RA Xi B., Cheng L., Jia J., Wang K., Ge J., Zhou M.;
RT "Cardiac functional improvement in rats with myocardial infarction by up-
RT regulating cardiac myosin light chain kinase with neuregulin.";
RL Cardiovasc. Res. 88:334-343(2010).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RX PubMed=15057822; DOI=10.1038/nature02426;
RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA Mockrin S., Collins F.S.;
RT "Genome sequence of the Brown Norway rat yields insights into mammalian
RT evolution.";
RL Nature 428:493-521(2004).
RN [3]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND DEVELOPMENTAL
RP STAGE.
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-155; SER-341 AND SER-422, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
CC -!- FUNCTION: Calmodulin-dependent kinase that phosphorylates MYL2 in
CC vitro. Promotes sarcomere formation in cardiomyocytes. Increases
CC cardiomyocyte contractility. {ECO:0000269|PubMed:17885681,
CC ECO:0000269|PubMed:20615916}.
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 -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:17885681}.
CC -!- TISSUE SPECIFICITY: Expressed in cardiomyocytes (at protein level). Up-
CC regulated in heart after experimental myocardial infarction at the mRNA
CC level. {ECO:0000269|PubMed:17885681, ECO:0000269|PubMed:20615916}.
CC -!- DEVELOPMENTAL STAGE: Up-regulated in the heart from 1 week after birth
CC through adulthood. {ECO:0000269|PubMed:17885681}.
CC -!- INDUCTION: by NRG1 (at protein level). {ECO:0000269|PubMed:20615916}.
CC -!- PTM: Phosphorylated on serine residues. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CAMK Ser/Thr
CC protein kinase family. {ECO:0000305}.
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DR EMBL; EU236721; ABW96144.1; -; mRNA.
DR RefSeq; NP_001104280.1; NM_001110810.1.
DR AlphaFoldDB; E9PT87; -.
DR SMR; E9PT87; -.
DR BioGRID; 253688; 1.
DR STRING; 10116.ENSRNOP00000023657; -.
DR iPTMnet; E9PT87; -.
DR PhosphoSitePlus; E9PT87; -.
DR jPOST; E9PT87; -.
DR PaxDb; E9PT87; -.
DR PeptideAtlas; E9PT87; -.
DR PRIDE; E9PT87; -.
DR Ensembl; ENSRNOT00000023657; ENSRNOP00000023657; ENSRNOG00000017546.
DR GeneID; 291926; -.
DR KEGG; rno:291926; -.
DR CTD; 91807; -.
DR RGD; 1305801; Mylk3.
DR eggNOG; KOG0032; Eukaryota.
DR GeneTree; ENSGT00940000160007; -.
DR HOGENOM; CLU_000288_90_0_1; -.
DR InParanoid; E9PT87; -.
DR OMA; DPWPLEE; -.
DR OrthoDB; 218222at2759; -.
DR TreeFam; TF314166; -.
DR PRO; PR:E9PT87; -.
DR Proteomes; UP000002494; Chromosome 19.
DR Bgee; ENSRNOG00000017546; Expressed in heart and 7 other tissues.
DR Genevisible; E9PT87; RN.
DR GO; GO:0015629; C:actin cytoskeleton; IEA:Ensembl.
DR GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR GO; GO:0005829; C:cytosol; IDA:BHF-UCL.
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; IMP:BHF-UCL.
DR GO; GO:0055003; P:cardiac myofibril assembly; IMP:BHF-UCL.
DR GO; GO:0071347; P:cellular response to interleukin-1; ISO:RGD.
DR GO; GO:0060298; P:positive regulation of sarcomere organization; IDA:BHF-UCL.
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:RGD.
DR GO; GO:0045214; P:sarcomere organization; IMP:BHF-UCL.
DR GO; GO:0048769; P:sarcomerogenesis; IMP:BHF-UCL.
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 ATP-binding; Cytoplasm; Kinase; Magnesium; Nucleotide-binding;
KW Phosphoprotein; Reference proteome; Serine/threonine-protein kinase;
KW Transferase.
FT CHAIN 1..786
FT /note="Myosin light chain kinase 3"
FT /id="PRO_0000419665"
FT DOMAIN 482..737
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 233..258
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 279..315
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 333..443
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 279..296
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 603
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 488..496
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 511
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:0007744|PubMed:22673903"
FT MOD_RES 341
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 422
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT CONFLICT 244
FT /note="T -> A (in Ref. 1; ABW96144)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 786 AA; 85541 MW; 3355DA69E4FCBB26 CRC64;
MSGVSEEDPE GLGPQGLPAL GGACLVTVDK KLNVLTEKVD RLLHFQEDVT EKLQCVCQGM
DHLEQGLHRL EASQELGLAG PGSTSPAAAQ AAWPEVLELV RAVRQEGAQH GARLEALFKM
VVAVDRAITL VGSTIQNSKV DDFILQGTVP WRKGSLADGP EENKEQAEVA GVKPKHVLNT
GSVQAATSRA LWEESQKQDT PVGTVEGLPL IIDTSLKGAD LTQAGASLRQ GVEALDPGQE
PPPTEAESRL PALASEDTGT TLELSVAIDR ISEVLTSLRM SQSAGEGTSS SKPDCSEPGP
QPLGPLTTDS DIHSDEGLPR ISVRMREMTT PEELFETQGG SPIGSAEAPG PGTVLEDQIP
KGARPFPPLP KRSCNNGGAS AEEATGPGAE PIRGPSLVTR DWRDEPVGTT DLQQGRDPGA
VSPEPGKDHA AQGPGRTEAG RRVSSAAEAA IVVLDDSAAP PAPFEHRVVS IKDTLISTSY
TVSQHEVLGG GRFGQVHRCT ERSTGLALAA KIIKVKNIKD REDVKNEINI MNQLSHVNLI
QLYDAFESKN SFTLIMEYVD GGELFDRITD EKYHLTELDV VLFTRQICEG VHYLHQHYIL
HLDLKPENIL CVSQTGHQIK IIDFGLARRY KPREKLKVNF GTPEFLAPEV VNYEFVSFPT
DMWSVGVITY MLLSGLSPFL GETDAETMNF IVNCSWDFDA DTFKGLSEEA KDFVSRLLVK
EKSCRMSATQ CLKHEWLNHL IAKASGSNVR LRSQLLLQKY MAQRKWKKHF HVVTAVNRLR
KFPTCP
